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CANCER RESEARCH INSTITUTE ANNUAL REPORT 2003 PAST IS PROLOGUE Contents Senior Staff 1 THE CRI STORY 11 MESSAGE FROM THE CHAIRMAN 13 HOW TO SUPPORT THE WORK 16 MAJOR PROGRAMS 21 SPECIFIC PROJECTS 24 ESPECIALLY GENEROUS DONORS 37 THE CRI LEADERSHIP 42 FINANCIAL STATEMENTS Jill O’Donnell-Tormey, Ph.D. Executive Director Lynne A. Harmer Director of Special Events & Grants Administration Joseph A. Isahack Network & Systems Manager Alfred R. Massidas Controller & General Manager MaryLee Thorne Director of Development National Headquarters 681 Fifth Avenue New York, NY 10022-4209 Tel. 212-688-7515 Fax 212-832-9376 Toll-free 1-800-99CANCER E-mail [email protected] www.cancerresearch.org Volunteer Offices 12011 San Vicente Boulevard Los Angeles, CA 90049 Tel. 310-471-2720 101 University Avenue, 4th Floor Palo Alto, CA 94301 Tel. 650-365-6441 184 Fisher Avenue Brookline, MA 02445 Tel. 617-566-0100 754 Walker Road, 2nd Floor Great Falls, VA 22066 Tel. 703-759-0835 THE CANCER RESEARCH INSTITUTE STORY CANCER RESEARCH INSTITUTE 1 “At the end of two weeks the neck tumor had disappeared...”-Dr. William B. Coley Dr. William B. Coley (1862-1936) was a prominent New York City surgeon from the 1890s until the 1930s. The success of his pioneering vaccine against certain types of cancer has earned him recognition as “the father of cancer immunotherapy.” His great-grandson, Geoffrey O. Coley, is a Trustee on the CRI Board. Immunology is recognized today as the most promising area of cancer research, and the Cancer Research Institute is leading the way. If you had predicted this in 1953, when CRI was founded, you would have been considered naive. Immunology was immature, and cancer immunology in particular was regarded with doubt by the medical establishment. The emergence of cancer immunology and CRI against great odds is a drama that began over a century ago, when Dr. William Coley, a young New York City surgeon, observed an amazing fact: in cancer patients who summoned the resources to fight off severe operating-room infections, tumors sometimes melted away. Could the patients’ stiffened powers of resistance also be fighting off the cancer? On May 3, 1891, Coley inaugurated the field of cancer immunology by injecting a culture of heat-killed bacteria into a hopelessly ill patient named Zola, who had a fist-sized neck tumor. Encouraged by an improvement in the man’s condition, Coley tried different culture preparations until he got the reaction he hoped for. “The tumor of the neck began to break down on the second day,” he wrote in his diary. “At the end of two weeks the neck tumor had disappeared…” Mr. Zola went on to live another 81⁄2 years. Coley refined his methods, creating a fluid known as “Coley’s toxins,” which produced many more apparent cures. “I went through 15,000 letters and papers...he’d never thrown away a thing!” -Helen Coley Nauts CANCER RESEARCH INSTITUTE 3 You might think he would have been hailed as a Louis Pasteur. Such was not the case. The basic reason is that his successes were unpredictable and inexplicable, since almost nothing was known about the immune system. This would remain true for decades to come. In addition, after “a few physicians, with indifferent preparations of the toxins,” as Dr. Coley put it, “failed to obtain good results,” the approach was quickly dismissed by medical journals. The dismissal was duly noted. Hospitals and the doctors who worked in them were dedicated to surgery, soon to be joined by radiation, and eventually, chemotherapy, to create a trinity of accepted practice. A friendly medical director of the hospital where Coley worked once confided to him that doctors there were allowed to “go out of their way, almost maliciously, to deprecate the toxins.” Dr. Coley enjoyed a successful career as a surgeon, but “Coley’s toxins” were marginalized, never to receive proper clinical testing (see p. 12)—and the appeal of cancer immunology as a subject worthy of talented researchers was seriously dimmed. Helen Coley Nauts (1907-2001) co-founded CRI with Oliver R. Grace (1909-1992) to advance the work begun by her father, Dr. William Coley. She was the first woman of science since Dr. Marie Curie to win the National Institute of Social Sciences’ Gold Medal for Distinguished Service to Humanity. Imagine a well-bred young woman who attends Miss Porter’s School in Connecticut, studies landscape design, marries a banker, then settles down to raise children and do volunteer work. Could she possibly have a place in our story? Yes, if her name is Helen Coley Nauts. After the death of her father, Dr. William Coley, Helen Coley Nauts discovered a daunting jumble of his records inside the family barn in 1938. “I went through 15,000 letters and papers in two years,” she later said. “He’d never thrown away a thing!” As she slowly brought the material into order, she realized that her father had made a genuine medical breakthrough. The idea ignited her, and she resolved to present it convincingly to the world. Helen Nauts taught herself biology and oncology, tracked down patients who had received “Coley’s toxins” to learn the long-term results, and sought out cancer doctors who were familiar with the treatment. Someone once asked her why her efforts were so untiring: “People are dying when I’m not working,” she replied. Meetings with doctors and patients were getting sizable by the early 1950s. The philanthropist Oliver Grace, a childhood friend, came forward with his wife, Lorraine: Why not meet at their large East Side Manhattan apartment? “Helen brought the doctors,” recalls Lorraine Grace, “and we supplied the spaghetti dinners.” In 1953, armed with meticulous analyses of 1,000 “Coley’s toxins” cases and the advice of open-minded oncologists, Helen Nauts and Oliver Grace co-founded 4 CANCER RESEARCH INSTITUTE the Cancer Research Institute. Its mission: to promote the field pioneered by Dr. Coley. Its initial budget: $15,000. Over the next 20 years, CRI gained recognition as the clearinghouse for information on cancer immunology, conducting a worldwide correspondence. It published monographs of Helen Nauts’ data compilations, so precise that they are still consulted by cancer researchers for clues about the disease. The Institute’s network of scientists and doctors grew, and with the help of a small circle of generous friends like the Graces, Julian Robertson, Anna-Maria and Stephen Kellen, and William Murray, it was able to support an increasing number of research projects. The workings of the immune system, as complex as a grand symphony, were slowly becoming better understood; cancer immunology made some advances, too. For example, scientists found that when cancer was induced in laboratory mice, the surface of the tumor cells bore characteristic bits of protein, called antigens, which could immunize other mice against transplants of the tumors. On the other hand, medical institutions (as well as their funding sources) still put their faith mostly in surgery and chemotherapy. The reputation of cancer immunology was not helped when, in 1965, “Coley’s toxins” were officially blacklist- For the past half century, Lorraine Grace has been a great friend of CRI, co-founded by her late husband, Oliver R. Grace; their early support helped to quickly establish the Institute as a respected effort. She serves on the CRI Board of Trustees along with her son, Oliver R. Grace, Jr. ed, together with apricot-pit extract and mistletoe, as a questionable treatment. Julian Robertson, now a Vice Chairman of the CRI Board of Trustees, remembers those days well. ”How many good cancer-immunology teams were there in the world then? Five or six at most.” Fortunately, one of those teams included a farsighted researcher named Dr. Lloyd Old. In 1967, CRI awarded an initial grant to Dr. Old, who hoped to discover whether antigenic reactions similar to those in mice also occurred in man. He had a larger vision, too. Turning the promise of immunotherapy into life-saving reality would take “Helen brought the doctors to our apartment and we supplied the spaghetti dinners.” - Mrs. Oliver(Lorraine) Grace -Mrs. Oliver (Lorraine) Grace CANCER RESEARCH INSTITUTE 5 “How many good cancer-immunology teams were there? Five or six at most.” -Julian H. Robertson, Jr. Philanthropist Julian H. Robertson, Jr., shown above circa 1974, joined the CRI Board in 1968; he became President in 1974, when Oliver Grace was named the first Board Chairman, and is currently a Vice Chairman. He is Founder and Chairman of Tiger Management, which grew into the world’s largest hedge-fund group. a broad, long-term effort. Much still had to be learned first about how the immune system recognized and attacked foreign substances. CRI’s medical advisors were impressed. While the Institute had begun with a focus on Dr. Coley’s work, it had steadily moved deeper into immunology, and needed a first-rate immunologist to lead it. In 1971, Dr. Old was appointed CRI’s medical director. He set out at once to expand CRI’s scope, bringing many of the world’s most distinguished immunologists, including Nobel Prize winners, to the Institute’s Scientific Advisory Council. It became a body that could speak with unimpeachable authority. He also persuaded the Board of Trustees to establish a new Postdoctoral Fellowship Program that would attract outstanding young scientists to immunology. Half the year’s budget was invested in the program—the first of several, which, to date, have helped more than 2,750 immunologists at universities, research centers, and hospitals worldwide. 6 CANCER RESEARCH INSTITUTE “The Nixon declaration of a ‘War on Cancer’ encouraged some unrealistic expectations.” -Lloyd J. Old, M.D. The 1970s and 1980s were exciting, turbulent times in cancer research. After President Nixon signed the National Cancer Act, the disease became a hot topic in the media; lucrative potential “cures” and “star” researchers made the covers of newsmagazines, only to be virtually forgotten in a year. “The Nixon declaration of a ‘War on Cancer’ encouraged some unrealistic expectations,” says Dr. Old. More than one observer has remarked on the almost manic-depressive way that immunological substances like interferon and interleukin-2 were greeted with enthusiasm, then prematurely discounted. As we now know, none of them is a “magic bullet,” but careful investigation has shown them to be of value under certain circumstances, or in combination with other treatments. The status of cancer immunology fluctuated with these ups and downs. Doubts were reinforced when experiments in the late 1970s found no evidence to support the widely accepted theory that the immune system constantly seeks out and destroys emerging cancer cells, and that tumors develop when this immunosur- Lloyd J. Old, M.D., shown above circa 1971, is Director of the CRI Scientific Advisory Council, Director and CEO of the global Ludwig Institute for Cancer Research, and a longtime researcher at Memorial SloanKettering Cancer Center. He and his colleagues have been making significant discoveries in tumor immunology since the 1960s. CANCER RESEARCH INSTITUTE 7 veillance fails. The theory has only recently been proved (see p. 23); an unsympathetic mind might have concluded that cancer immunology was fundamentally flawed. CRI Vice Chairman Carter Bales recalls those competitive days. “It was obvious,” he says, “that we had to reach out for a broader base of support.” While retaining the faithful core of supporters from its early years, CRI began a sustained communications program to inform the public and win additional funding; 30,000 new donors were gained between 1978 and 1982 alone. People saw As CRI President (1981-1984), Carter F. Bales, shown below circa 1981, worked closely with Chairman Oliver Grace to create a successful public-outreach effort. He is now a CRI Vice Chairman and Co-Managing Partner of the Wicks Group of Companies, L.L.C., a mediafocused private-equity firm. that CRI was championing a vital cause, virtually neglected by others. They appreciated the fact that, then as now, an uncommonly high percentage of the money they gave actually went to research. Competition for research talent was intensifying, too, at the same time as promising areas for investigation in immunology were opening up at an even faster rate. In 1986, CRI established the Investigator Award Program as a complement to its Postdoctoral Fellowships. “It was obvious we had to reach out for a broader base of support.” -Carter F. Bales 8 CANCER RESEARCH INSTITUTE The new program was designed to support accomplished assistant professors undertaking their first independent investigations in basic and tumor immunology— a challenging period that can determine the course of a career for years to come. “Immunology research needed a booster shot,” says Jacques Nordeman, who was CRI’s President at the time. “The Investigator Award delivered it.” CRI’s decades of investment in immunology paid significant dividends in the 1990s. Armed with deeper knowledge of the immune system’s basic workings, scientists were able to create techniques for identifying cancer antigens suitable for testing in vaccines. They learned how to construct many types of vaccines to deliver a given antigen, and developed methods to precisely monitor the results. As Dr. Lloyd Old had envisioned, the efforts now represented a broad, long-term commitment by immunologists from the USA, England, Germany, and France to Jacques C. Nordeman (CRI President, 1986-1991) helped develop the Investigator Award Program to invigorate the field of immunology. He is currently a Vice Chairman of the CRI Board of Trustees and Chairman of Nordeman Grimm, a leading executive-search firm. “Immunology research needed a booster shot; the Investigator Award delivered it.” -Jacques C. Nordeman CANCER RESEARCH INSTITUTE 9 “Cancer immunologists from around the world were finally on the same page.” -Donald J. Gogel Vice Chairman Donald J. Gogel became CRI President in 1991; after the death of Oliver Grace in 1992, he was appointed Chairman and served until 1997. He is President and CEO of Clayton, Dubilier & Rice, a long-established and respected private-equity investment firm. Russia and the People’s Republic of China…but one factor was missing. Coordination. With that need in mind, CRI initiated its International Symposia Series in 1994. These annual meetings convene researchers from dozens of countries and bring them up to the minute on progress in the field. “Cancer immunologists from around the world were finally on the same page,” notes CRI Vice Chairman Donald Gogel. The need for coordinating research efforts was even more critical. Research often consists of stand-alone projects that follow their own guidelines. Results are hard to compare and learn from. Proprietary interests get in the way of sharing those results. Thanks to the stature of the Scientific Advisory Council, CRI has been able to introduce a collaborative research model that brings together the best researchers from different institutions and focuses them on the most promising topics, using standardized methods and freely discussing their findings. Beginning in 1999, the model was first employed in what is now called the Cancer Antigen Discovery Collaborative, dedicated to identifying antigens in colon, breast, and prostate cancer. “The search for cancer cells’ weak points was speeded up through a team approach,” reports Vice Chairman Carlos Ferrer. 10 CANCER RESEARCH INSTITUTE “The search for cancer cells’ weak points was speeded up through the team approach.” -Carlos A. Ferrer As CRI entered the new millennium, the proven model was applied to tests of vaccines on actual patients, through our Cancer Vaccine Collaborative. Developed jointly with the Ludwig Institute for Cancer Research, the CVC unites a growing number of researchers in a worldwide quest that should ultimately uncover the basics of effective cancer immunization. Virtually every major research institution in the world now has scientists on staff who have been or are being funded by CRI, with fresh talent on the way. The journey begun by Dr. Coley isn’t over, but effective treatments appear to exist—a new vaccine to prevent cervical cancer, for example (see p. 32). Researchers are confident that in the foreseeable future, doctors will have a wide range of immunotherapies to save lives and reduce the need for drastic remedies. With your help, that day will be here sooner rather than later. During his Chairmanship of CRI (1997-2001), Carlos A. Ferrer was keenly involved in rolling out the Institute’s new collaborative research model. He is a Partner and Co-Founder of Ferrer Freeman & Company, a leading healthcare-focused privateequity firm. A MESSAGE FROM THE CHAIRMAN OF THE BOARD OF TRUSTEES CANCER RESEARCH INSTITUTE 11 “Our need for contributions here is what doctors call time-critical.” -Ann W. Jackson Ann W. Jackson, Group President of Time Inc. Women’s Group, has been Chairman of the CRI Board of Trustees since 2001; previously, she was a Trustee. Her commitment to CRI CRI’s budget has grown from $15,000 in 1953 to $15 million in fiscal 2003, a thousand fold increase. I can assure our donors that their money is well spent. Chemotherapy, radiation, and surgery are reaching their limits of efficacy. heightened dramatically when she Thanks largely to CRI, cancer immunology is moving rapidly out of the lab into the was diagnosed with breast cancer clinic, promising a new level of successful therapies…and CRI is the only organi- (prognosis excellent) in 1999. zation devoted to cancer immunology. Our need for contributions here is what doctors call time-critical. Donations are not salted away in a war chest, but go directly to underwrite current work that touches the lives of cancer patients today as well as in the future. Clinical trials of new vaccines on patients increased this past year as the CRIfunded Cancer Vaccine Collaborative expanded beyond New York City. This innovative team approach, developed by CRI and the Ludwig Institute for Cancer 12 CANCER RESEARCH INSTITUTE Research, now also involves the Mayo Clinic in Minnesota and institutions in Japan, Switzerland, Germany, and the U.K. in a powerful, united effort. Meanwhile, our Cancer Antigen Discovery Collaborative has isolated promising new antigens for the CVC to test in vaccines in the coming year. And our long-established commitment to nurturing talented immunologists was stronger than ever in 2003; we provided support for 248 grants at 98 institutions in nearly half the states and more than a dozen countries. I want to thank the especially generous donors who made this possible. Notably, The Atlantic Philanthropies continued its four-year, $20-million grant, which we leveraged to raise more gifts of $500,000-plus than ever before. Gratitude is also due to the CRI Board of Trustees. Board members made our fundraising events rousing successes—the Annual Awards Dinner netted a record $705,000—and their personal giving is at an all-time high. I want to welcome Heidi Ueberroth, Executive Vice-President of NBA Entertainment, and Frank V. Sica, Managing Partner of Soros Private Funds Management, who join CRI as new Board members, and say thanks to resigning members Richard S. Braddock, Chuck Scarborough, and Howard P. Berkowitz for years of service. We’re fortunate Howard will continue as an honorary Trustee and champion our Gar Reichman Fund. Past, they say, is prologue. This next year should be the most exciting yet for CRI and cancer immunology. Our fundraising goals have risen commensurately. We must further expand the CVC and CADC to keep up the momentum of discovery, without sacrificing our assistance to upcoming immunologists who will carry it into the future. One project of special interest: a possible test of “Coley’s toxins” (after a century of neglect) in a standardized manner, as an adjuvant or general immune-system booster in CVC trials. When Helen Nauts used to ask Dr. Lloyd Old why it took so long to do anything, he always replied: “Helen, it’s taken this many years for the science to catch up to your father’s vision.” I hope you’ll take a moment to look over the following pages and see how you can help complete the task. HOW TO SUPPORT THE WORK CANCER RESEARCH INSTITUTE 13 “The aim is to extract the maximum discovery from every dollar we receive.” -Jill O’Donnell-Tormey, Ph.D. Jill O’Donnell-Tormey holds a Ph.D. in cell biology and was a CRI Fellow at Rockefeller University before joining the Institute as Director of Public Information in 1987. She has served as Executive Director of CRI since 1993. Many Nobel Prize winners and members of the National Academy of Sciences believe that life-saving immunotherapies will be on hand for individual types of cancer within 10 to 15 years. There’s no better way to contribute to this end than by giving to CRI. The Institute is the acknowledged charitable leader in cancer immunology. Our Scientific Advisory Council actively shapes its course. And you can feel confident that your donation, in any amount, in any of the ways outlined below, will do the most good possible. In the most recent rating of charities by the American Institute of Philanthropy, called “the nation’s preeminent charities watchdog,” CRI was one of only two cancer organizations to receive an A+ for fiscal disclosure and integrity. This reinforces a reputation for financial commitment (recognized by Forbes magazine and many others) that goes back decades. During 2003, only 10 cents of every dollar we received went for the mechanics of fundraising and administration—a sense of priorities and efficiency of operation seldom matched by other cancer charities. As always, your gift is deductible for federal and state tax purposes as provided by law; CRI is tax-exempt under section 501(c)(3) of the IRS code. 14 CANCER RESEARCH INSTITUTE Outright Gifts Cash: Donations payable by check, money order, or credit card to the Cancer Research Institute immediately assist researchers all over the world; CRI’s Web site is equipped with a secure server for on-line contributions. Such gifts entitle you to the most generous charitable deduction. And donors who give $100 or more receive a year’s subscription to The Researcher, with news of CRI activities and developments in cancer immunotherapy. Property other than cash: Securities, real estate, automobiles, collectibles, and similar properties are a tax-efficient way to make meaningful gifts with little or no effect on current income. Workplace giving programs: Your company may have a payroll deduction plan through which you can contribute to CRI; ask your human resources department. CRI participates in the Combined Federal Campaign (member #0517), state and local government employee campaigns, and in corporate workplace giving as a member of the Community Health Charities Federation throughout the United States. We also participate in United Way Donor Choice programs. Matching gift programs: Many companies double or triple charitable donations made by their employees. Contact your human resources department to find out if your employer matches contributions. Planned Gifts The Cancer Research Institute is a living monument to its founder, Helen Coley Nauts. Appropriately, we have created the Helen Coley Nauts Society to acknowledge those who carry on her legacy by including CRI in their financial and estate plans. The most common gift of this kind is a bequest made through a living trust or inclusion of CRI in your will as a beneficiary of cash, securities, real estate, or personal property. Your bequest should include CRI’s federal tax ID number (131837-442) and a statement such as the following: “I bequeath to the Cancer Research Institute, Inc., a not-for-profit corporation of the State of New York, having its principal office at 681 Fifth Avenue, New York, New York 10022, the sum of $ _____ for its general corporate purposes.” Bequests can take a variety of forms, including specific dollar amount bequests, residuary bequests, and contingent bequests. CANCER RESEARCH INSTITUTE 15 The Helen Coley Nauts Society also includes those who name the Institute as a beneficiary of their life-insurance policy, retirement plan, or lead trust; who make a life income gift through a charitable gift annuity or charitable remainder trust; or who establish an endowment. Many of these “planned gifts” can offer donors tax advantages and income benefits while allowing them to do more for CRI. You should, of course, always consult your attorney and tax adviser for the formal writing of your will and to discuss the tax implications of any form of planned giving. Special-Purpose Giving Memorials and special occasions: You can make an outright or planned gift in memory of a relative, friend, or colleague, and CRI will send an announcement of the gift to whomever you specify. A donation of this sort can also serve as a tribute in recognition of a birthday, anniversary, or other milestone. Designated support: Although contributions for general purposes are especially welcome, you may wish to support a specific area of our work. Gifts can be designated for any of CRI’s programs, which are listed beginning on p. 16, or for regional research funds. You may prefer to designate a fellow or investigator for support. Postdoctoral Fellowships and Investigator Awards can be named in memory or in honor of a loved one. An annual donation of $45,000 over a three-year period supports a fellow; a four-year annual commitment of $50,000 per year supports an investigator, and $75,000 per year for three years supports investigators participating in the Cancer Vaccine Collaborative. Benefactors receive yearly research progress reports and are acknowledged in papers published about the work they have supported. To help you, your company, or your client make the most fitting and fulfilling contribution to CRI, please call MaryLee Thorne, our Director of Development, at 1-800-99CANCER or e-mail her at mar [email protected]. “Building the field of cancer immunology meant thinking at least a decade ahead.” -Lloyd J. Old, M.D. MAJOR PROGRAMS CANCER RESEARCH INSTITUTE 17 More than 30 years ago, CRI introduced its Postdoctoral Fellowship Program at the urging of Dr. Lloyd J. Old, to answer the long-term need for researchers who would build the future of cancer immunology. We now provide funding at every level of inquiry, from coordinated clinical trials to the most basic research, and support scientists at all career levels. In addition to highly competitive research grants awarded selectively by our Scientific Advisory Council, we sponsor a seminal international symposium on cancer immunology each year; educate the public about immunology and immunotherapy; and present awards to scientists and laypersons who have made outstanding contributions to the field. The following programs form the core of CRI’s commitments. RESEARCH PROGRAMS Predoctoral Emphasis Pathway in Tumor Immunology: The Predoctoral Emphasis Pathway was initiated in 1998 in order to capture the interest of talented researchers at the earliest stage. Through this program universities may apply for training grants that support doctoral students planning to pursue a career in cancer immunology. A seven-person panel including Scientific Advisory Council members and outside reviewers selects recipients of this grant, which provides $450,000 over a four-year period. CRI awarded two grants in fiscal 2003. Postdoctoral Fellowship Program: In 1971, the Postdoctoral Fellowship Program was established to support and train young immunologists at leading universities and research centers around the world. A panel of 14 scientists drawn from our Scientific Advisory Council rigorously evaluates each candidate, the intended sponsor and training environment, and the nature and feasibility of the proposed project. At a 2001 ceremony honoring Lloyd J. Old for 30 years of service as Director of the Scientific Advisory Council, Chairman Carlos Ferrer cited Dr. Old’s provident efforts to bring talented scientists into immunology as a key reason why he is “the true lifeblood and visionary for this organization.” Fellowship appointments are for three years. The stipend for new fellows is $40,000 for the first year, $42,000 for the second, and $44,000 for the third. A yearly allowance of $1,500 is provided to the host institution to help meet expenses for research supplies, travel to scientific meetings, and health insurance incurred on behalf of the fellow. In fiscal 2003, CRI awarded 33 fellowships for a total of $4.22 million. Investigator Award Program: The Investigator Award Program, established in 1986 to complement our Postdoctoral Fellowships, has supported 87 accomplished assistant professors undertaking their first independent investigations in basic and tumor immunology. By awarding these researchers $50,000 a year for a period of four years, the program provides flexibility and a degree of stability during this very challenging period. 18 CANCER RESEARCH INSTITUTE A seven-person panel including Scientific Advisory Council members and outside reviewers selects recipients of this prestigious award based on the applicant’s entire body of research rather than on a single project. In fiscal 2003, CRI awarded $1 million to support five new investigators. Clinical Investigation Program: The Clinical Investigation Program is composed of three distinct initiatives. Cancer Vaccine Collaborative: Created in partnership with the Ludwig Institute for Cancer Research, the CVC is an innovative network of coordinated early-phase cancer vaccine trials at hospitals and medical centers around the world. These multiple, yet parallel trials, which use defined antigens, standardized treatment protocols, uniform monitoring methodologies, and centralized data collection, are providing comparable results that will teach us how to effectively immunize against cancer. In fiscal year 2003, grants totaling $2.2 million were awarded to investigators at the participating CVC sites. Cancer Antigen Discovery Collaborative: Mobilizes invited experts to work cooperatively on defined tasks toward a common goal of identifying the targets on cancer cells that can serve as the basis for vaccines and antibody therapies. Seventeen grants totaling $800,000 were awarded in fiscal 2003. Grants Program: Supports individual preclinical and clinical research in three specific areas: cancer antigen identification for vaccine and antibody therapies; characterization of the immune response to cancer antigens; and the fashioning of vaccine and antibody-based therapies for cancer. CRI awarded $1.27 million in fiscal 2003 to support five preclinical studies. Designated Grants Program: Under its Designated Grants Program, the Institute supports research projects for which, in most cases, funds have been specifically raised. Among the special categories through which designated grants are awarded are the following longstanding programs: AIDS Program: CRI provides funding to scientists investigating how the AIDS virus infects the cells of the immune system and how the virus can be deterred. Our commitment to AIDS research dates back to 1983 when we were among the first private research funding organizations to recognize the urgency of the emerging AIDS epidemic and to see the relationship of the disease to certain types of cancer. Current AIDS-related projects are supported through our established research programs. Concern Foundation Program: Since 1981, CRI and the Concern Foundation for Cancer Research of Beverly Hills, CA, have provided joint support to the laboratory of Dr. George Klein at the Karolinska Institute in Stockholm, Sweden. Dr. Klein is CANCER RESEARCH INSTITUTE 19 one of the world’s leading tumor biologists, having pioneered research into the role of the Epstein-Barr virus in causing Burkitt’s lymphoma (a type of cancer) and other diseases. Moreover, Dr. Klein’s laboratory has been a training center for a large number of outstanding scientists from Russia and other former Communist countries. Gar Reichman Program: Through the Gar Reichman Fund, CRI supports the work of Dr. Malcolm A.S. Moore, who heads the Gar Reichman Laboratory and holds the Enid A. Haupt Chair in Cell Biology at Memorial Sloan-Kettering Cancer Center in New York City. The Gar Reichman Foundation was established in 1971, in memory of Gar Reichman, to fund research on leukemia and other blood-related diseases. The foundation entrusted its funds to CRI in 1988. EDUCATIONAL PROGRAMS International Symposia Series: CRI’s International Symposia Series is a powerful means of shaping the future course of cancer research. CRI developed these annual meetings to focus attention on progress in cancer vaccines and antibody-based therapies, the two central approaches of cancer immunology. The tenth meeting in the series took place in fiscal 2003 and celebrated the launch of the Cancer Research Institute/Ludwig Institute for Cancer Research Cancer Vaccine Collaborative and highlighted the major advances in the field of tumor immunology that have laid the scientific foundation for this auspicious program. Specifically, the meeting focused on four topics (1) Cancer Immunosurveillance/Immunoediting; (2) Cancer Antigen Discovery; (3) Monitoring the Immunological Response to Human Cancer; and (4) Cancer Vaccine Development. More than 350 scientists and clinicians from around the world attended the three-day meeting. Public Information Program: As part of its Public Information Program, CRI answers public inquiries about the field of cancer immunology and helps locate clinical trials of immunotherapies through a medical database, the Physician Data Query (PDQ). PDQ is a computerized cancer-information service maintained by the National Cancer Institute (NCI). It offers general information about cancer, NCI’s recommendations for standard treatment at each stage of a cancer, as well as information about FDA-approved clinical trials. CRI makes no medical recommendations; we suggest that patients review information they receive with their physicians. CRI provides a reference guide, the Cancer Research Institute HelpBook: What To Do If Cancer Strikes. Its clear, eight-step format explains how to get the best possible medical care, how to access support services, and how to approach other 20 CANCER RESEARCH INSTITUTE matters, such as financial concerns. The HelpBook includes an extensive resource directory listing medical facilities and other organizations that can furnish assistance. We have also published two cancer-specific booklets, What To Do If Prostate Cancer Strikes (see below) and Conquering Melanoma. Free copies are available by calling 1-800-33CANCER. Prostate Cancer Initiative CRI’s Prostate Cancer Initiative is a highly targeted approach to the treatment of prostate cancer undertaken in partnership with corporations and other nonprofit agencies, including the American Cancer Society and the National Prostate Cancer Coalition. In addition to funding research through the Clinical Investigation Program, the Initiative concentrates on patient support and education. Patient Support and Education: CRI funded the nationalization of the American Cancer Society’s patient support group program, Man-to-Man. It provides a forum for men diagnosed with prostate cancer to learn about the disease in an environment that encourages them to discuss their concerns and share solutions to common problems. In fiscal 2003, CRI awarded $50,000 to the National Prostate Cancer Coalition for the “Drive Against Prostate Cancer,” a national mobile screening and education campaign. The mobile screening unit, owned by Thor Industries, tours the country and to date has provided more than 20,000 men with free prostate cancer screenings. The Institute continues to build awareness through the wide distribution of its booklet, What To Do If Prostate Cancer Strikes. ANNUAL AWARDS William B. Coley Award for Distinguished Research in Immunology CRI grants the Coley Award to one or more scientists for outstanding achievements in basic immunology and cancer immunology. The award was established in 1975 in honor of Dr. William B. Coley, the acknowledged “father of cancer immunotherapy,” whose daughter, the late Helen Coley Nauts, founded the Cancer Research Institute. Oliver R. Grace Award for Distinguished Service in Advancing Cancer Research The Institute’s Grace Award recognizes the contributions of dedicated laypersons whose leadership has had a significant impact on cancer research. The award is named in memory of Oliver R. Grace, the founding chairman of CRI, who died in 1992. SPECIFIC PROJECTS CANCER RESEARCH INSTITUTE 21 July 1, 2002 - June 30, 2003 During fiscal 2003, CRI funded more than $10 million worth of training and research with grants at 98 institutions in 22 states and 14 countries—an effort that truly knows no boundaries. Our congratulations go out to all recipients, along with high hopes for their productive careers. Predoctoral Emphasis Pathways in Tumor Immunology Harvard Medical School, Boston, MA Harvey I. Cantor, M.D., and Hidde L. Ploegh, Ph.D. Program Coordinators Johns Hopkins University School of Medicine, Baltimore, MD Drew M. Pardoll, M.D., Ph.D. Program Coordinator Peter MacCallum Cancer Insititute, University of Melbourne, and Ludwig Institute for Cancer Research, Melbourne, Australia* Mark J. Smyth, Ph.D. Program Coordinator The Rockefeller University, New York, NY Michel C. Nussenzweig, M.D., Ph.D. Program Coordinator University of Colorado Health Sciences Center, Denver, CO Philippa C. Marrack, Ph.D. Program Coordinator University of Pennsylvania, Philadelphia, PA Yvonne Paterson, Ph.D., M.Sc. Program Coordinator University of Washington School of Medicine, Seattle, WA Christopher B. Wilson, M.D. Program Coordinator Washington University School of Medicine, St. Louis, MO Robert D. Schreiber, Ph.D. Program Coordinator Weill Medical College of Cornell University, New York, NY Carl F. Nathan, M.D., and Alan N. Houghton, M.D. Program Coordinators Immunology/Tumor Immunology Courses Alberto Martin, Ph.D. Role of chromatin remodeling in Ig V region hypermutation Brigham and Women’s Hospital, Boston, MA Mary E. Keir, Ph.D. The role of PD-1 in peripheral tolerance and tumor rejection Carme Roura-Mir, Ph.D. T-cell immunosurveillance of CD1cpresented dolichyl glycolipids in transformed cells “The Third Millenium” in Immunology, Tumor Immunology and Cancer Research* Moscow State University, Moscow, Russia Sergei A. Nedospasov, Ph.D., D.Sc. Course Coordinator Brown University, Providence, RI Marc Y. Dalod, Ph.D. Regulation of innate and adaptive immune responses to viral infections: Role of the cross-talk between NK cells and APC Winter School in Immunology Taj Fort Aguada, India Pramod K. Srivastava, Ph.D. Course Coordinator The Burnham Institute, La Jolla, CA Shihao Chen, Ph.D. Stucture and function of L-section ligands Postdoctoral Fellowships Wilfried K. Roth, M.D. The role of DEDD proteins in apoptosis and cancer Albert Einstein College of Medicine, Bronx, NY Peter R. Lawson, Ph.D. Molecular basis of lipid antigen recognition by CD1 restricted NKT cells Ziqiang Li, Ph.D.* Role of mismatch repair in somatic hypermutation and recombination in B cells California Institute of Technology, Pasadena, CA Yongning He, Ph.D.* Three-dimensional EMK studies of IgG transport by FcRn The CBR Institute for Biomolecular Research, Boston, MA Stefano Casola, M.D. Role of Epstein-Barr virus encoded LMP1 and LMP2a proteins in an animal model for Hodgkin’s disease 22 CANCER RESEARCH INSTITUTE Stefan Feske, M.D. Cloning and characterization of the gene responsible for a defect in capacitative calcium entry in patients with a severe combined immunodeficiency Sin-Hyeog Im, Ph.D. Role of calcineurin/NFAT signaling in generation and function of IL-10 producing regulatory T cells Alexandra M. Joseph, Ph.D. Activated notch1 expression in germinal center B cells: A potential model of classical Hodgkin’s disease Children’s Hospital, Boston, MA Nava Almog, Ph.D. Molecular mechanisms which underlie the heterogeneity of angiogenic activity in a tumor Oliver R. Grace Jr. Fellowship Columbia University College of Physicians & Surgeons, New York, NY Qinglian Liu, Ph.D.* Structural analysis of Hsp70 chaperone activity Dana-Farber Cancer Institute, Boston, MA Mei-Ling Chen, Ph.D. An animal model for investigating immunosurveillance and immunotherapy in prostate cancer Loralee J. Haughn, Ph.D. Characterization of Bc1-2 and cRaf1 as effectors for notch1 in T-cell lineage choice Hyuk Song, Ph.D. The role of tetraspanin, A15/TALLA-1 and CD151-like molecules in cancer biology Emory University, Atlanta, GA Shane Crotty, Ph.D. B-cell memory: Understanding the long-lived plasma cell Donald R. Latner, Ph.D.* The role of cell cycle genes in CD8+ memory T-cell homeostasis David B. Masopust, Ph.D. Disturbing the dynamics of adaptive immunity Edward J. Wherry, Ph.D. Temporal gene expression during T-cell exhaustion and deletion Fred Hutchinson Cancer Research Center, Seattle, WA Joseph N. Blattman, Ph.D. Enhancing CD8 T-cell responses to tumors and viruses by dominantnegative inhibition of Cbl-b function Benjamin J. McFarland, Ph.D. The NKG2D/MIC interaction: Initiating an immune response against carcinomas Xueling Wu, Ph.D.* Identification and characterization of HIV-1 envelope sequences that elicit broad neutralization antibody response Harvard Medical School, Boston, MA Marianne L. Boes, Ph.D. An EGFP-class II knock-in: A new tool for visualization of MHC class II trafficking in professional antigen Robert E. Means, Ph.D. Molecular mechanisms of KSHV K5 gene-mediated immune evasion Harvard School of Public Health, Boston, MA Michael J. Townsend, Ph.D. Investigating the molecular mechanisms of T cell lineage commitment: Isolation of T-β target genes and cytotoxic T-cell specific transcription factors Harvard University, Cambridge, MA Jeffery D. Cruzan, Ph.D. Detailed structural study of a transcription activator-coactivator complex: The CBP/p300-NFκB interaction Sarah M. McWhirter, Ph.D. Characterization of a novel IκB kinase complex Yingxia Wen, Ph.D. Mechanisms regulating the activation of a cluster of interferon-α and -β genes in response to virus infection Johns Hopkins University School of Medicine, Baltimore, MD Camie W.Y. Chan, Ph.D.* Development of a novel antigen-specific immunotherapy for cancers using genetically-modified dendritic cells generated in vivo via bone marrow transplantation of virally-transduced hematopoietic stem/progenitor cells Rajneesh P. Uzgare, Ph.D. Defining the role of B7-DC, a novel costimulatory molecule, in mediating immune response Joslin Diabetes Center, Boston, MA Reinhard Obst, Ph.D. Setting thresholds for T-cell development by regulated ZAP-70 expression in vivo Shannon J. Turley, Ph.D. Defining mechanisms of autoimmune disease initiation: Dendritic cells and the presentation of pancreatic β-cell antigens La Jolla Institute for Allergy and Immunology, San Diego, CA Laurent Gapin, Ph.D. Identification of the non-classical MHC class I molecule(s) involved in the selection of TcRαβ+ CD8αα+ intestinal intraepithelial lymphocytes Massachusetts General Hospital, Boston, MA Gabriel D. Duda, D.Md., Ph.D. Elucidating the extent to which bone marrow cells contribute to tumor growth: Potential for cancer therapy Christine J. Williams, Ph.D. The role of ikaros and the Mi2 β NURD chromatin remodeling complex in lymphocyte development and lymphomagenesis Massachusetts Institute of Technology, Cambridge, MA Kelly M. Elkins, Ph.D.* Analysis and design of Bcl-2 protein interactions Phillip David Holler, Ph.D.* Genetic and molecular characterization of a central tolerance defect in NOD mice Michael T. McManus, Ph.D. Mechanisms of mammalian RNA interference McGill University, Montreal, Canada Annie Bourdeau, Ph.D.* Characterization of the hematopoietic and bone marrow stromal cell defects in T-cell protein tyrosine phosphatasedeficient mice Memorial Sloan-Kettering Cancer Center, New York, NY Don M. Coltart, Ph.D.* The development of immunologically based cancer therapeutics via chemical synthesis Katrina Podsypanina, M.D., Ph.D. Role of lymph nodes in metastatic cancer progression CANCER RESEARCH INSTITUTE 23 Robert D. Schreiber, Ph.D., an Associate Director of CRI’s Scientific Advisory Council, won the Institute’s prestigious William B. Coley Award in 2001 for research substantiating the theory of cancer immunosurveillance. He is the Alumni Endowed Professor of Pathology and Immunology and professor of microbiology at Washington University in St. Louis. “With CRI’s help, the controversy is over: immune cells unquestionably fight cancer.” -Robert D. Schreiber, Ph.D. Dori A. Thomas, Ph.D. Identification of the molecular mechanisms responsible for TGFβ-mediated inhibition of T-lymphocyte proliferation Mount Sinai Hospital, Toronto, Canada Bruce T. Seet, Ph.D.* Molecular and biological specificity of Grb2-like family proteins National Cancer Institute, Bethesda, MD Claudette L. Fuller, Ph.D. Regulatory role of the actin cytoskeleton in CTL activation National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD Alex Yee-Chen Huang, M.D., Ph.D.* Dynamic intravital imaging of tumorAPC-T-cell interactions Hai Qi, M.D., Ph.D.* A possible antigen-presenting role for dendritic cells in humoral as well as cell-mediated immunity: High-resolution imaging analysis in vitro and in vivo Helen C. Su, M.D., Ph.D.* Molecular function of caspase-8 in lymphocyte activation New York University School of Medicine, New York, NY Natacha Bitton, Ph.D. Potential of infection by DC sign, a dendritic cell protein and its interest as a vaccine target Thomas O. Cameron, Ph.D.* A comparative study of the oligomeric state of the T-cell receptor Arash Grakoui, Ph.D. The role of CD+ T cells in hepatitis C virus pathogenesis Ontario Cancer Institute, Toronto, Canada Thorsten Berger, Ph.D. In vivo analysis of ADAM10 signaling in p53 pathways, cancer formation, and the innate immune system Young B. Kim, Ph.D. Specific gene activation during Stat3mediated cellular transformation Rhea (Rose Marie) Finnell Memorial Fellow Almut Dufner, Ph.D. Identification and analysis of PTEN regulator and effector molecules Vuk Stambolic, Ph.D. Molecular analysis of PTen-induced lymphoid tumors in vivo Woong-Kyung Suh, Ph.D. The role of a novel B7-related molecule B7RP2 in the immune system Peter MacCallum Cancer Insititute, Melbourne, Australia Yoshihiro Hayakawa, Ph.D.* NKT cells in anti-tumor responses: Conductors of tumor immunity? Princeton University, Princeton, NJ Dapeng Zhou, M.D., Ph.D. Natural glycolipid ligands of CD1d molecules The Rockefeller University, New York, NY Simi T. Ahmed, Ph.D.* Molecular mechanism of Stat3mediated transformation Xiaodi Ren, Ph.D. Role of B-cell specific coactivator OCAB in B-cell differentiation Evelyn B. Voura, Ph.D. Bone marrow transendothelial migration of multiple myeloma cells Xin Yu, M.D., Ph.D. Functional characterization of isoforms of a B-cell specific coactivator The Scripps Research Institute, La Jolla, CA Amanda L. Gavin, Ph.D. B-cell responses to T-independent type 2 antigen Kaisa H. Holmberg, M.D., Ph.D. TCR dimerization during antigen recognition Stanford University School of Medicine, Stanford, CA Erin J. Adams, Ph.D. Structural biology of ligand recognition by T-cell receptors Deepta Bhattacharya, Ph.D.* Characterization of the hematopoietic niche (cont’d. page 30) “You know you’re doing something clearly very important when you give to CRI.” -Anna-Maria Kellen Our sincere gratitude goes out to the individuals, corporations, and foundations acknowledged here for their especially generous support of CRI in 2003. While money alone doesn’t equal a “cure” for cancer, the effective immunotherapies now seen on the horizon will certainly elude our grasp without it. We also thank the members of the Helen Coley Nauts Society, also acknowledged on the following pages; they are helping to safeguard our future work by naming the Institute as the beneficiary of a bequest or planned gift. Anna-Maria Kellen and her husband, Stephen, Co-Chairman of the international banking firm Arnhold and S. Bleichroeder Holdings, Inc., are two of New York City’s most generous philanthropists. Mrs. Kellen has served as a CRI Trustee for more than 40 years, and received the 2003 Oliver R. Grace Award. ESPECIALLY GENEROUS DONORS CANCER RESEARCH INSTITUTE Mr. and Mrs. Martin J. Bergin Coley Pharmaceutical Group Michael Berkman and Randi Ribakove Communicator Inc. The Estelle Abas Trust Mr. and Mrs. Howard P. Berkowitz Community Hearing Instruments III Abbott Laboratories Fund The Judy and Howard Berkowitz Concern Foundation Major Donors Mr. and Mrs. Richard J. Adler Foundation Cliff P. Connery and Maryanne Friedel The Altschul Foundation Berlex Laboratories, Inc. Mr. and Mrs. John J. Connor Edith M. Amateau Mr. and Mrs. Edgar R. Berner Lottie M. and Charles H. Cook American Express Company Bernstein Investment Research and Corporate Risk Solutions, LLC American Legacy Foundation Management Madeleine G. Corson Amgen Inc. Edith C. Blum Foundation, Inc. Daniel Cripe A. W. Anderson Foundation Tor Boswick Frances L. and Edwin L. Cummings E. M. Anderson Foundation Steven Bowman Kathleen C. Andrews Estate of Barbara Brown Boyer Mr. and Mrs. Maurice J. Cunniffe Anonymous (10) Mr. and Mrs. Richard S. Braddock Mr. and Mrs. John P. Curran Michael Anthony Mr. and Mrs. Oren Bramson Mr. and Mrs. John R. Curtis, Jr. Anthony For Men L.L.C. Mr. and Mrs. Timothy J. Brennan Mr. and Mrs. Rodd Dalinka Antigenics LLC Mr. and Mrs. Conrad L. Bringsjord Mr. and Mrs. Stuart P. Davidson Aon Foundation Bristol-Myers Squibb Company Richard M. DeMartini and Jennifer L. Nancy Arena Broadgate Consultants, Inc. The Atlantic Philanthropies Brown Investment Advisory & Trust Aureole Investment, L.P. Company Memorial Fund Brorsen DeMartini Family Foundation Burton & Beatrice Dermer Family Foundation, Inc. Avon Foundation John C. Bruce Peter Axelrod & Associates, P.C. Mr. and Mrs. Michael C. Buchanan Mr. and Mrs. Philip Desantis Mr. and Mrs. Carter F. Bales Llewellyn Burchell Charitable Trust Mr. and Mrs. Glenn J. DeSimone Alissa Beth Bander Memorial Mr. and Mrs. Charles L. Burnett John W. Dickey Mr. and Mrs. John P. Callahan Rita and Harold Divine Foundation Bank of America Ruth Camp Campbell Foundation Helen and Bruce Dixon Banta Direct Marketing Group Cardinal Health Healthcare Marketing Nestor Dominguez Foundation, Inc. Joseph M. Barber Services Barclays Bank, PLC Estate of Pandora Rudland Carroll The James E. and Jacob A. Barkey Russell L. Carson Lynn Trunz Dominick Robert Lee Douglas and Elizabeth A. Strode John and Pamela Casaudoumecq Mr. and Mrs. Richard C. Dresdale Mr. and Mrs. Kenneth Barmore The Cayuga Foundation Cathy Duffy The Florence & Ben Barrack Mr. and Mrs. Christopher E. Chalsen James Dunne Chapdelaine Corporate Securities & Eckerd Corporation Foundation Memorial Fund Foundation Inc. Mr. and Mrs. Michael G. Barrett Co. John Eckerson The Barrington Foundation Charina Foundation, Inc. Estate of Dorothy M. Eiser Rose Barrow Russell and Katherine Charlton Richard A. Eisner Brian L. Bartlett Citigroup Global Markets, Inc. Eli Lilly and Company Estate of Etta Baum David C. Clapp Foundation Mrs. Richard B. Englund Bear, Stearns & Co., Inc. Clayton, Dubilier & Rice, Inc. Essence Communications, Inc. Timothy P. Beaulac Cline, Davis & Mann, Inc. Estron Chemical, Inc. Everett A. Bell William H. Coffee Trust Daniel Eule Estate of Germaine Benesch Mr. and Mrs. Geoffrey O. Coley Exxon Mobil Corporation 25 26 CANCER RESEARCH INSTITUTE Estate of Mary S. Fadeley Green Charitable Foundation, Inc. Kaye Scholer LLP Sean Fahey Green Family Foundation Kekst and Company Incorporated FannieMae Joyce Green Family Foundation Kelco Landscaping, Inc. Mr. and Mrs. Thomas M. Farley, Jr. GreenPoint Foundation Anna-Maria & Stephen Kellen Mr. and Mrs. Vincent Farrell, Jr. Christine Gunner Fashion Bug Mary Gurster William M. Kelly Andrew and Mindy Feldman Haffenreffer Family Fund Estate of Blanche C. Kelly Mr. and Mrs. Carlos A. Ferrer Hagedorn Fund Rene M. Kern Ferrer Freeman & Company LLC Philip J. Hahn Estate of Elsie E. Kiel Nazareth Festekjian Bruce D. Haims and Judy Jackson David B. Kinney Jerrold & Sally Fine Foundation, Inc. Neita Harrigan F.M. Kirby Foundation, Inc. Warren J. Finnell Harvest Charities Mr. and Mrs. David M. Kittay Ramin Firoozye Estate of Margaret Hayman Mr. and Mrs. Michael Klein Mr. and Mrs. John B. Fitzgibbons Mr. and Mrs. Donald B. Hebb, Jr. Robert E. Kling Christopher Fitzmaurice Mr. and Mrs. William Heinzerling Mark Kopcha Fitzpatrick, Cella, Harper & Scinto Estate of Fredrick Charles Henne KPMG LLP Fleet Bank The Carl J. Herzog Foundation Estate of Sidney G. Ladue Foote Cone & Belding Edward A. Hewett and Margaret A. C. Linda Lambert 2001 Separate Mr. and Mrs. William E. Ford III Heyob Foundation Property Trust Ford Foundation Mr. and Mrs. John Howitt Mr. and Mrs. Leigh R. Lasky Mr. and Mrs. James A. Forese Robert Huffman Mr. and Mrs. Carey F. Lathrop Max & Clara Fortunoff Foundation ICON Clinical Research, Inc. Gregory P. Lee Anthony Frangione Pat Ihlenburg James B. Lee, Jr. Freygish Foundation International Equity Advisors LLC The Florence & Edgar Leslie Fribourg Family Foundation J.V. Sports Gambrell Family Foundation Mr. and Mrs. Charles W. Jackson Mr. and Mrs. Gary J. Gartner Mary L. Jacob Lawrence M. Gelb Foundation, Inc. The Benjamin Jacobson and Sons General Atlantic Partners Foundation CharitableTrust James Annenberg Levee Charitable Foundation Les Levi Anne Boyd Lichtenstein Foundation Estate of Mildred Gentry Mr. and Mrs. Robert J. Jacobson Mr. and Mrs. Rich Lightburn Gibbs & Associates The Jesselson Foundation Vincent S. Lima Regina Gilmour Charitable Remainder Jockey Hollow Foundation, Inc. Fran Liner Kupferman Trust Margaret Ann Johnson The Bari Lipp Foundation Mr. and Mrs. Jay T. Glassman Mr. and Mrs. Thomas S. Johnson Lord & Taylor Mr. and Mrs. Donald J. Gogel Johnson & Johnson L'Oreal USA Laurie and Jeffrey Goldberger JPMorgan Chase & Company Richard Ray Loucks and Ruth M. Philip Goldblatt Charitable Trust The J.P. Morgan Chase Foundation John G. & Jean R. Gosnell Foundation, Inc. Matching Gift Program Loucks Fund Mr. and Mrs. Leroy W. Lovelidge III Estate of Doris Kabat Mr. and Mrs. Alexander P. Lynch Janet Maureen Grace Committeeship David Kampff Sally & Alex Lynch Fund Mrs. Oliver R. Grace Merherwan K. Kandawalla Mrs. Eleanor D. MacCracken Oliver R. Grace Charitable Foundation Robert S. Kaplan The Maher Family Foundation Mr. and Mrs. Robert M. Grace The Kastory Family Foundation Mr. and Mrs. Tom Maheras Granite Broadcasting Corporation Marion Esser Kaufmann Foundation Estate of Henrietta Malbin CANCER RESEARCH INSTITUTE Mr. and Mrs. Ronald M. Mateo Mr. and Mrs. Joseph C. O'Connor Mr. and Mrs. Julian H. Robertson, Jr. Estate of Margaret Mazzey The O'Donnell Iselin Foundation, Inc. The Robertson Foundation The MBNA Foundation Lloyd J. Old, M.D. Mr. and Mrs. Ralph W. Rose Lynn Glenn McAtee Mr. and Mrs. Stephen Oplinger Eric Rosen Helen G. Spencer McDermid Ortho Biotech Lief D. Rosenblatt Mr. and Mrs. Patrick J. McGrath Peter B. Orthwein David Asher Rosenstein Mr. and Mrs. Robert M. McKeon Paul and Anna Oschwald Trust Mr. and Mrs. Jonathan Roth McMullan Family Fund Mr. and Mrs. John Ostrander Mrs. Edmond J. Safra Medical Action Communications, USA Estate of Marjorie W. Packwood The Sage Foundation Medicus Group International, Inc. Debbie Pappas Mr. and Mrs. Daniel J. Salmon Thomas G. and Andrea Mendell The Partridge Foundation Salomon Smith Barney Andrew M. Paul Family Foundation Stanley and Jane Sapery Mr. and Mrs. Eugene Mercy, Jr. Peale Foundation Mr. and Mrs. Christopher J. Sarkis Estate of Nancy J. Merkel George W. Peck IV Jack Scanlon Merrill Lynch & Co., Inc. PerkinElmer Foundation Mr. and Mrs. Michael E. Schultz Mr. and Mrs. Michael Meyers Jeffrey A. Perlowitz Mr. and Mrs. Henri Axel Schupf Millennium Pharmaceuticals, Inc. Steve Peterson The Edith M. Schweckendieck Trusts Mr. and Mrs. Mark G. Miller Mr. and Mrs. Leland A. Peyser Estate of Harold Bend Sedgwick Robert Miller Pfizer Inc Gillian Z. Segal and Peter Lattman Mr. and Mrs. Robert K. Miller David C. Pichler Tasha Seitz Rory Millson and Linda E. Rodd Pielsticker Charitable Lead Annuity Select Equity Group Foundation Foundation Estate of Alex Mitchell Trust Michael Charles Sharp The Ambrose Monell Foundation Estate of Harriet-Anne Pierson Mr. and Mrs. Donald Shaw Montgomery, McCracken, Walker & Estate of Dorothy Plumb Eric P. Sheinberg Foundation Estate of Nick J. Pokea Mr. and Mrs. David M. Shepherd Mr. and Mrs. Robert A. Posner Renee and Irwin Shishko Mr. and Mrs. Edwin Damron Poulton Shubert Foundation, Inc. Sarah Mott Price Family Foundation Estate of Belle V. Silverstein Estate of Alexander Munchweiler PriceWaterhouseCoopers Simpson Thacher & Bartlett Robert A. Murray Estate of Dorothy S. Pritchard The Simpson Foundation Mutual of America Joseph J. Provenzano Linda and Stephen L. Singer Fund Gregory R. Myers Mr. and Mrs. Jeremy Purbrick Estate of Jean V. Sirles Naomi Myers John E. Purcell Mr. and Mrs. Ernest B. Smith Carey Nachenberg Mr. and Mrs. James B. Quigley Mr. and Mrs. James C. Smith The Nash Family Foundation, Inc. Mr. and Mrs. Matthew Quigley Estate of Ruth Sneve Sergei A. Nedospasov, Ph.D., D.Sc. The Raether Family 1985 Charitable Soros Fund Charitable Foundation Rhoads, LLP Morgan Stanley Dean Witter Foundation The New York Academy of Medicine Trust Mark Stein Mr. and Mrs. Matthew Nimetz Random Real Estate Mr. and Mrs. James Stern Estate of Geneva W. Nolen James Ransohoff, Jr. Mr. and Mrs. Richard B. Stolley Mr. and Mrs. Jacques C. Nordeman Dr. Barbara Ray Estate of Myrtle B. Summers Novartis Oncology Roma Reavis-Wehde Estate of John J. Supon Ardavan Nozari The Reese Charitable Remainder Surefire Marketing, Inc. Estate of Dorothy B. Nurick Harry A. & Margaret M. Oak Charitable Lead Trust Trust Swansea Holy Ghost Brotherhood Mr. and Mrs. James Remick Mr. and Mrs. Josh Tane Mr. and Mrs. Brian Riano Mr. and Mrs. Mitchell J. Taube 27 28 CANCER RESEARCH INSTITUTE Lee Asher Betty Disbrow Belle Asherman Adelaide J. Dodge Mr. and Mrs. George D. Thurston Else Baier Blanche Elizabeth Eckerts Time Life, Inc. Olga Baker Dorothy M. Eiser Krista Tommarello Marion D. Balen Ruth Engelberg Mr. and Mrs. Remy W. Trafelet Jeanne E. and Jacob A. Barkey Nathan Epstein Mr. and Mrs. Robert S. Trump Mr. and Mrs. Kenneth Barmore Max G. Eriksen Tullett & Tokyo Investment Corp. Florence and Ben Barrack Juanita M. Evans UBS Investment Bank Rose Barrow Mary S. Fadeley Ueberroth Family Foundation Etta Baum Helen Jean Falk Union Pacific Frank L. Bell Herbert Lynn Fann The Uplands Foundation Germaine Benesch Florence A. Fanning Nancy and Jim Utaski William A. Berkey Carlos A. Ferrer Estate of Zelda M. Uthe Herta J. Bernstein Adelaide E. Ferris Mr. and Mrs. Jeffrey K. Valentine Grace M. Bishop Paul Fierro Vance Van Dine John Bittel Clay Frazier Steven R. Victorin Guy Bjorkman Alice M. Fried Antone L. Vinelli Irrevocable Trust Leslie J. Blain Zoltan Galdi Mr. and Mrs. John Vissichio Lawrence H. and Nancy E. Bonander Salvador Garcia Thomas M. Von Lehman and Mary Borbeck Stella Gentile Wade F.B. Thompson Charitable Foundation, Inc. Robina C. Bouchard Mildred Gentry Steve Wagman Barbara Brown Boyer Penelope M. Georgiadis WellPoint Health Networks Lucille Brents Janet Gifford Mr. and Mrs. Robert M. Wepfer Victor E. Broll Regina Gilmour Mr. and Mrs. William T. Whamond Albert N. Brooks Eleanor Goldberg Gerald I. White Fund Minnie E. Brown Norman Gottlieb Whiting Foundation Virginia Bruner Joseph Junior Greathouse Estate of Saul J. Wiener Alfred R. Brunner Jeanine Hair Mr. and Mrs. Richard Wilkes Cleo F. Bush Nelle B. Haire Wyeth Joy Biggs Buttle Loretta D. Hardy Mr. and Mrs. Thomas M. Yamin Tracy Campbell Evelyn H. Harris Stephen Yegelwel Angela Carbone Ottis C. Harris Estate of Marion E. Youngberg Alfred Carlucci Helaine T. Harrison Mr. and Mrs. Ronald F. Zampolin, Jr. Julia Carlucci James Leon Hawkins Peter Zdazenski Pandora Rudland Carroll Margaret Hayman Mr. and Mrs. Ronald M. Zimmerman Donald O. Carswell Virginia Hemme Melba Case Fredrick Charles Henne William H. Coffee Senora Henry Gwendolyn Colburn Kay Hilton Lottie M. and Charles H. Cook Grace M. Humphrey Estelle Abas Eleanor H. Cromley Fred W. and Idell E. Iltner Peter Adams Vincent D'Amico Ruby R. Jankiewicz Frederick Allard Annabelle L. Danzig Eldon and Lynn Jasper Ruth Ascher Aileen Adele Delong Warren R. Jecklin Rex and Virginia Ashdown Emma Deters Doris M. Johnson Margaret M. Good Helen Coley Nauts Society CANCER RESEARCH INSTITUTE Doris Kabat Ezilda Michel Renee and Irwin Shishko Bertha E. Kaufman Helen T. Middleton Katherine U. Silva Samuel Kay Ruth Miller Belle V. Silverstein Blanche C. Kelly Alex Mitchell Augusta Simon Elsie E. Kiel Janet P. Morgan Roma Sinclair Theresa A. Kiely Stella Moss Estelle Singer Hilda Kirson Alexander Munchweiler Jean V. Sirles Ruth Klotz Judith K. Murphy Paul Slat Anne Koch Kathryn T. Murphy Catherine M. Smith Josephine M. Krska Thomas P. Murray Mr. and Mrs. Ernest B. Smith Murray Kupferman Thomas Murry Ruth Sneve Rose Lachow Naomi Myers Fred E. Spencer Sidney G. Ladue Alice A. Nauts W. M. Sprenger Anna Lagstein Rose E. Nelson Brenda M. St. James C. Linda Lambert Freda E. Newton Gerald J. Steinberg Ann Lancet Geneva W. Nolen Leopold Steindecker Marguerite Landis Dorothy B. Nurick Daniel B. Stern Caryl Lou Langford Harry A. and Margaret M. Oak Myrtle B. Summers Elizabeth S. Larkin Michele A. Ognibene John Supon James F. Levens Lauri Olsen Carl E. Thomas Betty Lou Levin Alice Orlich George C. Thomas, Jr. Beatrice Levy Paul and Anna Oschwald Overton Arnold Thompson Johanna Loeb Lilly E. Pace Viola Mae Thompson Peter Lommen Marjorie W. Packwood John R. and Anita Timmel Delia Luna Andrew Reid Paton Carola S. Trier Kay Lungo Frederick V. Payne Zelda M. Uthe Norma Lyon Nancy Elizabeth Pease Josephine S. Villeman Eleanor D. MacCracken Rose Perry Antone L. and Myrtle H. Vinelli Emilie Machalinski Agnes Phelps Anne D. Vinton Catriona Macleod John Piercy Ethel A. Wagner David Madsen Harriet-Anne Pierson David Walker Henrietta S. Malbin Dorothy Plumb Julia Walz William S. Mardenborough Nick J. Pokea Irene M. Watkins Aljoe Martin Despina Poulos Dorothy Waugh Isolde K. Martin Mrs. P. Prasad Albert L. and Ione A. Weickert Raleigh L. Martin Dorothy S. Pritchard Vera White Evelyn Masdonati Helen Relkin Saul J. Wiener Mildred G. Matz Floris J. Renk Ora Brown Windle Margaret Mazzey Veronica A. Rose Nettie Wright Michael I. McBride Susan Rosenberg Ethel R. Young Annette McDonald Hedwig Salzer Marion E. Youngberg J. Donald McKinney, Jr. Lydia B. Scannell Gloria Zaino Jan Mears Helen R. Schutt Grace Muriel Mecchi Ruth Schwartzman Nancy Jeanne Merkel Rev. Harold Bend Sedgwick 29 30 SPECIFIC PROJECTS (cont’d.) Camilla Forsberg, Ph.D. Chromatin remodeling in stem-cell differentiation Emmanuel Niels Treiner, Ph.D.* Mechanisms of natural killer cells selftolerance Martha S. Jordan, Ph.D. The role of SLP-76 domains in thymocyte development and T-cell function Tara Maureen C. Hornell, Ph.D. GM-CSF-mediated regulation of class II MHC antigen presentation in human monocytes Xingxing Zang, Ph.D. PD-1 mediated inhibition in T-cell responses: Molecular mechanisms and manipulation in tumor immunotherapy Wei-Xing Zong, Ph.D. Roles of c-Myc and Akt protooncogenes in lymphocyte metabolism and apoptosis Johannes B. Huppa, Ph.D. Defining the mechanism that links ligand-recognition by αβ TCR to T-cell activation University of California, Los Angeles, CA Caius G. Radu, M.D. The role of the lysophospholipid receptor G2A in immunological tolerance University of Texas Southwestern Medical Center at Dallas, Dallas, TX Gaya K. Amarasinghe, Ph.D. Structural basis for regulation of guanine nucleotide exchange activity of the DBL homology domain from the protooncogene product VAV Ji-Yun Kim, Ph.D. Rho GTPases in chemattractantstimulated adhesion Michael S. Kuhns, Ph.D. TCR-mediated events in immunological synapse formation Karina L. McQueen, Ph.D. Human natural killer cell receptor reconstitution and alloreactivity following allogeneic bone marrow transplantation Sang-Ho Park, Ph.D. Cross-regulation between the Wnt signaling and T-cell activation University of California, San Diego, La Jolla, CA Carl S. Goodyear, Ph.D. Superantigen induced cell death in leukemic B cells Li-Chung Hsu, Ph.D. The mechanism of IKK/NF-κB and p38 MAPK signaling pathways synergizing to suppress apoptosis in activated macrophages University of Virginia, Charlottesville, VA Donald R. Drake, Ph.D. Mechanisms of incomplete CD8+ lymphocyte activation Zhi-Wei Li, Ph.D. The role of IKK-β in lymphoid leukemia and lymphoma Kevin L. Legge, Ph.D.* Role of respiratory dendritic cells in the adaptive immune response to pulmonary infections Achal M. Pashine, Ph.D. Accessory molecules in the class II presentation pathway: Structure and function University of California, San Francisco, CA Victoria L. Crotzer, Ph.D. The role of clathrin in T-cell receptor internalization and MHC class I target recognition on tumor cells University Hospital Basel, Basel, Switzerland Mark A. Daniels, Ph.D.* Defining the affinity threshold for positive and negative T-cell selection Tianhe Sun, Ph.D.* The roles of NK activating receptors and their ligands in host defense University Hospital Zurich, Zurich, Switzerland Nicola Harris, Ph.D. Allergy and the gut University of California, Berkeley, CA Samantha Jane Allen, Ph.D.* The structure and function of chemokine receptors Philippe Bousso, Ph.D. Dissection of thymocyte selection events at the single cell level Nadine C. Fernandez, Ph.D. Self tolerance of natural killer cells: The role of NK hyporesponsiveness Tsvetelina P. Pentcheva, Ph.D. Mechanism of regulation of T-cell function by CD28 and CTLA-4 David M. Morgan, Ph.D. Mechanism of WASP activation by Cdc42 University of Chicago, Chicago, IL Yuval Sagiv, Ph.D.* Glycolipid antigen presentation by CD1 molecules: Role of endosomal saposins University of Cologne, Cologne, Germany Markus Müschen, M.D. Rescuing pre-apoptotic germinal center B cells: The role of the Epstein-Barr virus in early steps of the pathogenesis of Hodgkin’s disease University of North Carolina at Chapel Hill, Chapel Hill, NC Raquel Sitcheran, Ph.D. Investigating the role of NF-κB in cell differentiation and oncogenesis University of Pennsylvania, Philadelphia, PA Ezequiel M. Fuentes, Ph.D. Regulation of B-cell development by the BCR components of Ig α and Ig β Angela L. Zarling, Ph.D. Phosphorylated peptides associated with MHC molecules identification, immunogenicity and use as tumor antigens Washington University School of Medicine, St. Louis, MO Eric Sean Barton, Ph.D. Role of host antiviral molecules in murine gammaherpesvirus 68 pathogenesis Jack D. Bui, M.D., Ph.D. The role of natural killer cells in tumor surveillance and rejection Hiroaki Ikeda, M.D., Ph.D.* Identification of novel tumor-specific antigens in fibrosarcomas derived from RAG2-/- immunodeficient mice John Hans Old and Edna Alice Old Memorial Fellow Olga V. Naidenko, Ph.D. Stuctural basis of promiscuous ligand recognition by the natural killer cell activating receptor NKG2D Lyse A. Norian, Ph.D.* Tumor progression and aging: Combined effects on the anti-tumor response CANCER RESEARCH INSTITUTE Nigel D.L. Savage, Ph.D. CD43: A critical regulator of T-cell motility and activation Whitehead Institute for Biomedical Research, Cambridge, MA Matthew G. Guenther, Ph.D.* Dissection of the NF-κB transcriptional regulatory network in human macrophages I-hung Shih, Ph.D. Tiny regulatory RNAs in hematopoiesis: A possible link to hemotological diseases Emily C. Walsh, Ph.D.* Genetic analysis of host susceptibility to human immunodeficiency virus and acquired immunodeficiency syndrome Yanping E. Lu, Ph.D. Mechanistic studies and antiviral functions of interferon-inducible human guanylate-binding proteins Yehuda Matza, Ph.D.* The role of a novel giant proteinAHNAK2 in calcium signaling in the immune system Charalambos G. Spilianakis, Ph.D.* Protein and chromatin modifications required for the expression of the IL-4 gene during TH1/TH2-cell differentiation Yisong Y. Wan, Ph.D.* Characterize the roles of Smad4 in T-cell function 31 Brigham and Women’s Hospital, Boston, MA D. Branch Moody, M.D.* Activation of human dendritic cells for CD1-mediated lipid antigen presentation to T cells California Institute of Technology, Pasadena, CA Jose Alberola-Ila, M.D., Ph.D. Analysis of the signals that control T cell fate determination Columbia University College of Physicians & Surgeons, New York, NY Raphael A. Clynes, M.D., Ph.D. Indentification of cellular effectors and molecular mechanisms of FcRmediated ADCC in vivo Investigator Awards The Wistar Institute, Philadelphia, PA Sandra E. Lavens-Phillips, Ph.D. Regulation of Epstein-Barr virus reactivation in B lymphocytes Yale University School of Medicine, New Haven, CT Ona E. Bloom, Ph.D.* Function of neuronal proteins at the immunological synapse Aimin Jiang, Ph.D.* E-cadherin/catenin signaling and the control of dendritic cell function Koichi Kobayashi, Ph.D. Analysis of the CARD carrying kinase gene in vivo Baylor College of Medicine, Houston, TX Jin Wang, Ph.D. Roles of caspase-10 in initiating apoptosis signaling Zheng Zhou, Ph.D. Recognition and phagocytosis of apoptotic cells Beth Israel Deaconess Medical Center, Boston, MA Masayuki Noguchi, M.D., Ph.D. Molecular characterization of protooncogene TCL1 as an Akt kinase coactivator Danila Valmori, Ph.D. Use of MHC class I/peptide multimers incorporating tumor antigen-derived peptides for dissecting the interactions between MHC/tumor antigen complexes and specific T-cell receptors Dartmouth Medical School, Hanover, NH Charles Sentman, Ph.D. NK-cell recognition and activation against tumor metastasis “We see very encouraging immune responses in the trials supported by CRI.” Ellen Puré, Ph.D., an Associate Director of the Scientific Advisory Council and Chairman of the Fellowship Committee, also sits on the committee that selects the CVC participants and reviews and monitors the program’s clinical trial protocols. She is a professor at the Wistar Institute in Philadelphia and Director of the Office of Academic Review at the Ludwig Institute for Cancer Research. -Ellen Puré, Ph.D. 32 CANCER RESEARCH INSTITUTE CRI-funded scientist Ian Frazer, M.D., developed the methods used to create a new vaccine that could prevent nearly half of all cases of cervical cancer, which kills nearly 300,000 women each year. He is Director of the Center for Immunology and Cancer Research, Princess Alexandra Hospital, at the University of Queensland, Australia. “This new vaccine that prevents cervical cancer grew out of research funded by CRI.” -Ian Frazer, M.D. Deutsches Krebsforschungszentrum, Heidelberg, Germany Stefan Eichmüller, Ph.D. Characterization and evaluation of a new tumor-specific antigen for immune therapy of cutaneous T-cell lymphoma and other malignancies Elaine R. Shepard Memorial Investigator Duke University Medical Center, Durham, NC Tannishtha Reya, Ph.D.* Control of hematopoietic stem-cell development Fred Hutchinson Cancer Research Center, Seattle, WA Cassian Yee, M.D. Augmentation of immune response to melanoma Karolinska Institute, Stockholm, Sweden Petter Höglund, M.D., Ph.D. Dissecting the mechanisms of natural killer cell tolerance Krankenhaus Nordwest, Frankfurt, Germany Elke Jäger, M.D. New SEREX-defined cancer antigens, T-cell responses and implications for specific cancer immunotherapy Partridge Foundation Investigator Ludwig Institute for Cancer Research, Lausanne, Switzerland Frédéric Lévy, Ph.D. Factors influencing the generation of CTL-defined peptide tumor antigens Ludwig Institute for Cancer Research, New York, NY Ali O. Güre, M.D., Ph.D. CT antigens in cancer: Mechanism of SSX gene expression and identification of genes with restricted tumor expression Libby Bartnick Memorial Investigator Mayo Clinic, Rochester, MN Daniel D. Billadeau, Ph.D. Regulation of anti-tumor immunity by Rho-GTPase effector pathways Mount Sinai School of Medicine, New York, NY Patricia Cortes, Ph.D. In vitro V(D)J recombination: Signal and coding joint formation during inversional recombination Gwendalyn J. Randolph, Ph.D. Differentiation and migration of monocyte-derived dendritic cells and their role in immunity: Comparison to other dendritic cell subsets Northwestern University, Evanston, IL Theodore S. Jardetzky, Ph.D. Structural studies of cell surface receptors of the immune system Oregon Health & Science University, Portland, OR Qing Ching Chen, M.D. Receptor editing in self-reactive B lymphocytes: A mechanism of autoimmunity The Rockefeller University, New York, NY Madhav Dhodapkar, M.D. Optimizing immune responses to dendritic cells in humans The Scripps Research Institute, La Jolla, CA Christoph Rader, Ph.D. Generation and humanization of rabbit monoclonal antibodies for therapeutic targeting of the tumor vasculature Partridge Foundation Investigator Stanford University School of Medicine, Stanford, CA K. Christopher Garcia, Ph.D. Structural studies of the interleukin-6 receptor complex University of Chicago, Chicago, IL Ioannis A. Aifantis, Ph.D., M.Sc.* The BCL-2 family member A1 as a regulator of T-cell survival and transformation Guido Franzoso, M.D., Ph.D. The control of apoptosis by NF-κB University of Massachusetts Medical Center, Worcester, MA Cynthia A. Chambers, Ph.D. Immunoregulation of CTLA-4-/- T cells in vivo Francis Ka-Ming Chan, Ph.D.* Analysis of TNF receptor signaling in health and disease University of Michigan, Ann Arbor, MI Malini Raghavan, Ph.D. Molecular interactions in the MHC class I antigen presentation pathway CANCER RESEARCH INSTITUTE University of Oxford, Oxford, United Kingdom Vincenzo Cerundolo, M.D., Ph.D., MRCPath. Processing and presentation of melanoma CTL epitopes University of Washington School of Medicine, Seattle, WA Mark Bix, Ph.D. Regulation of cytokine gene expression Chen Dong, Ph.D.* Regulation of immune responses by novel costimulatory molecules Washington University School of Medicine, St. Louis, MO Robert H. Arch, Ph.D. TRAF-mediated signaling pathways regulating tumor cell apoptosis Barry P. Sleckman, Ph.D. Regulation of T-cell receptor gene rearrangement Clinical Investigation Program Cancer Vaccine Collaborative Columbia Presbyterian Medical Center, New York, NY Kyriakos P. Papadopoulos, M.D.†, and Charles Hesdorffer, M.Med. (1) Phase I study of NY-ESO-1 peptide immunization with GM-CSF of patients with tumors expressing NY-ESO-1 or LAGE-1; (2) A phase I study of peptidebased vaccine therapy in patients with high-risk or metastatic melanoma † Anna-Maria Kellen Clinical Investigator Krankenhaus Nordwest, Frankfurt, Germany Elke Jäger, M.D. Pilot study of immunization with ProteinD MAGE-3/His and/or NYESO-1 protein combined with CpG 7909 in patients with tumors expressing MAGE-3 and/or NY-ESO-1 and/or LAGE-1 Ludwig Institute for Cancer Research, New York, NY* Gerd Ritter, Ph.D. Development, manufacture, and characterization of mixed bacterial vaccine (Coley’s toxin) for clinical reevaluation in patients with cancer Mayo Clinic & Foundation, Rochester, MN* Svetomir Markovic, M.D., Ph.D. Dose finding study of aerosolized NYESO-1 peptide vaccine with/without GM-CSF administered as adjuvant therapy following complete tumor resection Memorial Sloan-Kettering Cancer Center, New York, NY Harry Herr, M.D., Dean F. Bajorin, M.D., Padmanee Sharma, M.D., Ph.D., Sacha Gnjatic, Ph.D. NY-ESO-1 protein immunization of postcystectomy patients with transitional cell carcinomas of the bladder expressing NY-ESO-1 or LAGE-1 antigen Jakob Dupont, M.D. Phase I study of NY-ESO-1b peptide plus Montanide in patients with ovarian, primary peritoneal, or fallopian tube cancer expressing NY-ESO-1 or LAGE-1 Robert Maki, M.D., Ph.D. A phase II study of anti-CTLA4 antibody in advanced synovial sarcoma patients with NY-ESO-1 or LAGE-1 expressing tumors Mie University School of Medicine, Mie, Japan* Hiroshi Shiku, M.D. (1) Phase I trial of immunization with HER2-derived peptide in HLA-A2402 patients with HER2-expressing cancers of the breast, ovary, stomach or lung; (2) Immunization with cholesteryl hydrophobized polysaccharide (CHP)HER2 protein complex in HLA-A2402positive patients with HER2-overexpressing cancers Mount Sinai School of Medicine, New York, NY Anna C. Ferrari, M.D. Pilot study of immunization with ProteinD MAGE-3/His and NY-ESO-1 protein combined with CpG 7909 in patients with high-risk stage D-1 or advanced prostate cancer expressing MAGE-3 and/or NY-ESO-1 and/or LAGE-1 New York University Cancer Institute, New York, NY Nina Bhardwaj, M.D., Ph.D., Steven Burakoff, M.D., and Susan Talbot, M.B.B.S.* A randomized controlled trial of melanoma treatment: Comparison of dendritic cells versus QS-21 as adjuvants to stimulate anti-tumor immunity Okayama University Medical School, Okayama, Japan* Eiichi Nakayama, M.D. NY-ESO-1 protein immunization of patients with tumors expressing NYESO-1 or LAGE antigen 33 Roswell Park Cancer Institute, Buffalo, NY Kunle Odunsi, M.D., Ph.D. (1) A pilot clinical trial of NY-ESO-1DP4 p157-170, a peptide of potentially dual MHC class I and class II specificities, in patients with epithelial ovarian, fallopian tube or primary peritoneal carcinomas whose tumors express NY-ESO-1 or LAGE-1; (2) Phase I study of recombinant vaccinia-NY-ESO-1 and recombinant fowlpox-NY-ESO-1 in patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express NY-ESO-1 or LAGE-1 antigen University Hospital Zurich, Zurich, Switzerland* Alexander Knuth, M.D., Dirk Jäger, M.D. Pilot study of immunization with proteinD MAGE-3/His and/or NY-ESO-1 protein combined with CpG 7909 in patients with tumors expressing MAGE3 and/or NY-ESO-1 and/or LAGE-1 University of Oxford, Oxford, United Kingdom Vincenzo Cerundolo, M.D., Ph.D., MRCPath. Pilot study of immunization with proteinD MAGE-3/His and/or NY-ESO-1 protein combined with CpG 7909 in patients with tumors expressing MAGE3 and/or NY-ESO-1 and/or LAGE-1 Weill Medical College of Cornell University, New York, NY Nasser K. Altorki, M.D. (1) Phase II trial of immunization with proteinD MAGE-3/His and immunological adjuvant AS02B in patients with non-small cell lung cancer; (2) Phase II study of NY-ESO-1 peptide plus GM-CSF immunization in patients with non-small cell lung cancer expressing NY-ESO-1 antigen; (3) Safety and immunological evaluation of NY-ESO-1 plasmid DNA (pPJV7611) cancer vaccine given by particle mediated epidermal delivery (PMED) in patients with NY-ESO-1 or LAGE-1 expressing non-small cell lung cancer; (4) A pilot study of NY-ESO-1b peptide plus CpG 7909 and Montanide ISA-51 in patients with advanced nonsmall cell lung cancer expressing NYESO-1 or LAGE-1 Cancer Antigen Discovery Collaborative Baylor College of Medicine, Houston, TX Rongfu Wang, Ph.D.* 34 CANCER RESEARCH INSTITUTE Columbia University College of Physicians & Surgeons, Ludwig Institute Clinical Trial Center, New York, NY Maha Ayyoub, Ph.D.* Danila Valmori, Ph.D.* INSERM, Nantes, France Francine Jotereau, Ph.D.* Institut für Zellbiologie, Tübingen, Germany Cecile Gouttefangeas, Ph.D.* Hans-Georg Rammensee, Ph.D.* Krankenhaus Nordwest, Frankfurt, Germany Elke Jäger, M.D.* Ludwig Institute for Cancer Research, Lausanne, Switzerland C. Victor Jongeneel, Ph.D.* Daniel Speiser, M.D.* Gregory Theiler* Ludwig Institute for Cancer Research, Melbourne, Australia Andrew M. Scott, FRCAP, DDU* Richard Simpson, Ph.D.* Ludwig Institute for Cancer Research, New York, NY Ali O. Güre, M.D., Ph.D.* Achim Jungbluth, M.D.* Matthew J. Scanlan, Ph.D.* Moscow State University, Moscow, Russia Dmitry Kuprash, Ph.D.* Sergei A. Nedospasov, Ph.D., D.Sc.* Okayama University Medical School, Okayama, Japan Eiichi Nakayama, M.D.* RIKEN BioResource Center, Tsukuba, Japan Yuichi Obata, Ph.D.* University Hospital Zurich, Zurich, Switzerland Dirk Jäger, M.D.* Alexander Knuth, M.D.* University of Oxford, Oxford, United Kingdom Vincenzo Cerundolo, M.D., Ph.D., MRCPath.* University of Saarland, Homburg, Germany Michael Pfreundschuh, M.D.* Christoph Renner, M.D.* University of Virginia, Charlottesville, VA Michael A. Coppola, Ph.D.* Weill Medical College of Cornell University, New York, NY Yao-Tseng Chen, M.D., Ph.D.* Grants Baylor College of Medicine, Houston, TX Rongfu Wang, Ph.D. Identification of prostate cancer antigens recognized by tumor-infiltrating lymphocytes Dana-Farber Cancer Institute, Boston, MA Ellis L. Reinherz, M.D. Thymic vaccination strategies as an approach to prevent prostate cancer Duke University Medical Center, Durham, NC Johannes Vieweg, M.D. A safety and feasibility study of active immunotherapy with metastatic prostate carcinoma using autologous dendritic cells pulsed with antigen encoded in amplified autologous tumor RNA Krankenhaus Nordwest, Frankfurt, Germany Elke Jäger, M.D. Phase I study of intensive course intralymphatic immunization with peptides derived from MAGE-1, MAGE-3, and/or NY-ESO-1 combined with GMCSF in patients with high risk stage D1 or advanced prostate cancer Leiden University Medical Center, Leiden, The Netherlands Sjoerd H. van der Burg, Ph.D. Detection and isolation of HPV-specific T helper cells, a preclinical study Loyola University Chicago, Maywood, IL Liang Qiao, M.D. Application of MHC tetramers to the measurement of HPV-specific CTL responses Ludwig Institute for Cancer Research, Lausanne, Switzerland Frédéric Lévy, Ph.D.* From cancer genomics to cancer immunotherapy Fondazione Centro San Raffaele Del Monte Tabor, Milan, Italy Maria Pia Protti, M.D.* Defining the helper epitope repertoire on tumor antigens to study the CD4+ T cells in neoplastic patients Massachusetts General Hospital, Boston, MA Martin Mihm, M.D., F.A.C.P. Tumor infiltrating lymphocytes and prognosis in human cutaneous melanoma The Hebrew University, Jerusalem, Israel Ofer Mandelboim, Ph.D. Immunological markers related to prostate cancer prognosis: Identification of ‘lysis ligands’ for human NK lysis receptors Memorial Sloan-Kettering Cancer Center, New York, NY Jedd D. Wolchok, M.D., Ph.D. Vaccination of AJCC stage III and IV melanoma patients with human and mouse tyrosinase DNA vaccines: A phase I trial to assess safety and immune response Infectious Disease Research Institute, Seattle, WA Steven G. Reed, Ph.D. Therapeutic vaccine studies with prostase Johns Hopkins University School of Medicine, Baltimore, MD Richard B. S. Roden, Ph.D. Cross-genotype neutralization of human papillomavirus and development of a broadly protective vaccine Kantonsspital St. Gallen, St. Gallen, Switzerland Marcus Groettrup, Ph.D. Identification of prostate carcinoma antigens by SEREX analysis and development of a PSA/PLGA anti-prostate carcinoma vaccine New York University School of Medicine, New York, NY Nina Bhardwaj, M.D., Ph.D. Immune response to antigen bearing dendritic cells in patients with resected stage III melanoma Vincent K. Tsiagbe, Ph.D. Role of retroviral superantigens in human lymphoma development Ohio State University, Columbus, OH Pan Zheng, M.D., Ph.D. Prostate cancer tissue resource Okayama University Medical School, Okayama, Japan Yuji Noguchi, M.D., Ph.D. Expression and immunogenicity of NYESO-1 in prostate cancer CANCER RESEARCH INSTITUTE 35 Steven J. Burakoff, M.D., is Director of the Skirball Institute of Biomolecular Medicine at the New York University School of Medicine and is the Director of the NYU Cancer Institute, recently selected as a participating CVC site. The CVC trials at NYU will be testing different vaccine formulations for the treatment of melanoma. “CRI’s Cancer Vaccine Collaborative is what we’ve been missing in this field.” -Steven J. Burakoff, M.D. Oregon Health & Science University, Portland, OR Janko Nikolich-Zugich, M.D., Ph.D. Heteroclitic CTL vaccination against prostate cancer University Hospital of Erlangen, Erlangen, Germany Gerold Schuler, M.D. Vaccination of HLA-A1, -A2 or -A3+ stage III/IV melanoma patients with tumor peptide-loaded autologous dendritic cells that are generated in the absence or presence of TRANCE/ RANK-L University of Alabama at Birmingham, Birmingham, AL Jiri Mestecky, Ph.D. Humoral immunity and cytokine production in HPV-induced cervical cancer University of California, Los Angeles, CA Linda Baum, M.D., Ph.D. Apoptosis resistance and immune evasion in prostate cancer: A novel role for galectin-1 University of Chicago, Chicago, IL Thomas F. Gajewski, M.D. Immunization with PSMA peptidepulsed autologous PBMC plus rhIL-12 University of Illinois at Chicago, Chicago, IL David J. Peace, M.D. Phase IB pilot trial of PSA-peptide based specific active immunotherapy in HLA-A2+ patients with prostate cancer University of Lausanne, Lausanne, Switzerland Jean-Pierre Mach, M.D. Development of a new cancer immunotherapy strategy using antitumor antibody fragments conjugated to antigenic MHC/peptide complexes University of Munich, Munich, Germany Gert Riethmüller, M.D. A multicenter study in minimal residual disease of prostate cancer: Prognostic significance of MAGE gene expression by disseminated tumor cells in bone marrow University of Pittsburgh Medical Center, Pittsburgh, PA John M. Kirkwood, M.D. Immunological therapy of melanoma Hassane M. Zarour, M.D. Phase I/II study of vaccination with CpG oligonucleotides (CpG 7909) alone, or the multi-epitope vaccine containing the NY-ESO-1 and the NY-ESO peptides alone, or the combination, in patients with metastatic measurable melanoma and other NY-ESO-1+ tumors University of Queensland, Queensland, Australia Ian Frazer, M.D., FRCPA Genotype specific and genotype cross reactive cell-mediated immunity to VLPbased papillomavirus vaccines; A phase I trial of virus-like particle immunotherapy for HPV-associated infection University of Rotterdam, Rotterdam, The Netherlands Reinder L.H. Bolhuis, M.D. Gerrit Stoter, M.D., Ph.D. Immuno-gene therapy of metastatic renal cell cancer patients University of Virginia, Charlottesville, VA William P. Irvin, Jr., M.D. Evaluation of the immunogenicity of vaccination with synthetic peptides mixed with GM-CSF-in-adjuvant, following surgical debulking, in patients with advanced ovarian cancer Craig L. Slingluff, M.D. The human immunotherapy program at the University of Virginia University of Washington School of Medicine, Seattle, WA Alexander Fefer, M.D. Immunological monitoring in vaccines for HPV-associated cervical cancer Wake Forest University, Winston-Salem, NC Zheng Cui, M.D., Ph.D.* Spontaneous regression of late-stage cancer in mice; Sequencing the candidate genes for the SR/CR mutation responsible for innate immune response to cancers in mice Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia Andreas Strasser, Ph.D. The role of BH3-only proteins in the control of cell death in the prostate 36 CANCER RESEARCH INSTITUTE Washington University School of Medicine, St. Louis, MO Paul M. Allen, Ph.D. Immunologic mechanisms of host response to prostate cancer: Immunotherapy of prostate cancer Peter Humphrey, M.D., Ph.D. Immunologic mechanisms of host response to prostate cancer: Immunologic regulation of scatter factor/hepatocyte growth factor during development of prostatic cancer Robert D. Schreiber, Ph.D. IFNγ and the development of protective immune responses to primary tumors: A new view of tumor immune surveillance; Immunologic mechanisms of host response to prostate cancer: Immunosurveillance in prostatic cancer Kathleen Sheehan, Ph.D. Immunologic mechanisms of host response to prostate cancer: Alterations in cellular sensitivity to IFNγ during development of prostatic tumors and metastases Weill Medical College of Cornell University, New York, NY Neil H. Bander, M.D. Phase I trial of 177Lutetium-DOTAhuJ591 in patients with hormonerefractory prostate cancer; Prostate cancer therapy with monoclonal antibody to prostate specific membrane antigen Designated Grants Beijing Cancer Hospital, Beijing, China Yu Wang, Ph.D.* Characterization of NY-ESO-1-specific CD8+ T cells from different lymph nodes and periphery blood of lung cancers Dana-Farber Cancer Institute, Boston, MA Lee Nadler, M.D. Generation of immunity to cancer Hadassah Medical Center, Jerusalem, Israel Aviram Nissan, M.D. Identification of molecular targets for immunotherapy in colorectal cancer University Hospital of Erlangen, Erlangen, Germany Gerold Schuler, M.D.* Sponsorship of the 7th International Symposium on Dendritic Cells University of Chicago, Chicago, IL Hans Schreiber, M.D., Ph.D. Immunological therapy and prevention of HIV-associated cancers Patient Support National Prostate Cancer Coalition, Washington, DC Support of the “Drive Against Prostate Cancer” Annual Awards Karolinska Institute, Stockholm, Sweden George Klein, M.D., D.Sc.* Studies on EBV, oncogenes, tumor suppressor genes and tumor immunology Willliam B. Coley Award Ludwig Institute for Cancer Research, Lausanne, Switzerland Monique Zahn, Ph.D.* Academy of Cancer Immunology’s online journal, Cancer Immunity Charles A. Janeway, Jr., M.D.* (1943-2003) Memorial Sloan-Kettering Cancer Center, New York, NY Malcolm A.S. Moore, D.Phil.* Analysis of telomerase gene expression in human cancer Jules A. Hoffmann, Ph.D.* CNRS Institute of Molecular and Cellular Biology Strasbourg, France Bruno Lemaitre, Ph.D.* CNRS Center for Molecular Genetics Gif-sur-Yvette, France Ruslan Medzhitov, Ph.D.* Yale University School of Medicine New Haven, CT Oliver R. Grace Award Hearn Jay Cho, M.D., Ph.D.* Vaccine immunotherapy for multiple myeloma Nagasaki University, Nagasaki, Japan Yasuhiro Nagata, M.D. Induction and analysis of CD8+ CD4+ T cells against cancer antigens in breast and colon cancer Strang Cancer Prevention Center, New York, NY Rache Simmons, M.D.* Rhea (Rose Marie) Finnell Breast Cancer Care Program Anna-Maria Kellen* Philanthropist and Cancer Research Institute Trustee Henry A. McKinnell, Jr., Ph.D.* Chairman of the Board and CEO Pfizer Inc *Awarded in fiscal year 2003 THE CRI LEADERSHIP “CRI has nurtured cancer immunology from tantalizing observations into a -Herbert F. Oettgen, M.D. truly modern science.” Herbert F. Oettgen, M.D., has served on the CRI Scientific Advisory Council since 1971, playing a significant role in expanding its scope. He is currently an Associate Director of the Council and a Member of the Immunology Program at Memorial Sloan-Kettering Cancer Center. SAC meeting, early 1970s; left to right: Lloyd Old, Helen Nauts, Edmund Klein, Robert Good, Herbert Oettgen, and Edward Boyse. 38 THE SCIENTIFIC ADVISORY COUNCIL The Scientific Advisory Council is composed of distinguished scientists from 13 countries who guide the development of cancer immunology without politics or bottom-line pressure. They include 4 Nobel Prize winners, 24 members of the National Academy of Sciences, and 23 members of the Academy of Cancer Immunology. The Council’s universally respected judgment is put into effective action through the power of the purse; all CRI funding decisions, from predoctoral training awards to grants for clinical trials, are arrived at in deliberation by Council members. Director Lloyd J. Old, M.D.2,3,5,6 Ludwig Institute for Cancer Research New York, New York Associate Directors Glenn Dranoff, M.D.3 Dana-Farber Cancer Institute Boston, Massachusetts Carl F. Nathan, M.D.3,4 Weill Medical College of Cornell University New York, New York Herbert F. Oettgen, M.D.3 Memorial Sloan-Kettering Cancer Center New York, New York Benvenuto G. Pernis, M.D.4 Columbia University College of Physicians & Surgeons New York, New York Ellen Puré, Ph.D.4,6 The Wistar Institute Philadelphia, Pennsylvania; and Ludwig Institute for Cancer Research New York, New York Robert D. Schreiber, Ph.D.3,4,5,6 Washington University School of Medicine St. Louis, Missouri Richard Axel, M.D.2 Columbia University College of Physicians & Surgeons New York, New York Baruj Benacerraf, M.D.1,2 Dana-Farber Cancer Institute Boston, Massachusetts Sir Walter F. Bodmer, Ph.D., F.R.S.2 Hertford College Oxford, England Thierry Boon, Ph.D.3 Ludwig Institute for Cancer Research Brussels, Belgium Edward A. Boyse, M.D.2 University of Arizona Tucson, Arizona Harvey Cantor, M.D.2 Dana-Farber Cancer Institute Boston, Massachusetts Jean-Charles Cerottini, M.D.3 Ludwig Institute for Cancer Research Lausanne, Switzerland Peter Cresswell, Ph.D.2,4 Yale University School of Medicine New Haven, Connecticut Jean Dausset, M.D.1,2 Fondation Jean Dausset CEPH Paris, France Members Garry I. Abelev, Ph.D.3 Russian Cancer Research Center Moscow, Russia Emil Frei III, M.D. Dana-Farber Cancer Institute Boston, Massachusetts Gideon Goldstein, M.D., Ph.D. Thymon, LLC Short Hills, New Jersey Philip D. Greenberg, M.D.3,4 University of Washington School of Medicine and Fred Hutchinson Cancer Research Center Seattle, Washington Jordan U. Gutterman, M.D. The University of Texas M.D. Anderson Cancer Center Houston, Texas Sen-itiroh Hakomori, M.D., Ph.D.2 University of Washington School of Medicine Seattle, Washington Karl Erik Hellström, M.D. Pacific Northwest Research Foundation Seattle, Washington Richard J. Hodes, M.D. National Institute on Aging Bethesda, Maryland Alan N. Houghton, M.D.3 Memorial Sloan-Kettering Cancer Center New York, New York John M. Kirkwood, M.D. Pittsburgh Cancer Institute University of Pittsburgh Medical Center Pittsburgh, Pennsylvania George Klein, M.D., D.Sc.2,3 Karolinska Institute Stockholm, Sweden Alexander Knuth, M.D.3,6 University Hospital Zurich Zurich, Switzerland John Kuriyan, Ph.D.2 University of California, Berkeley, California Richard A. Lerner, M.D.2 The Scripps Research Institute La Jolla, California Dan R. Littman, M.D., Ph.D. New York University School of Medicine New York, New York Tak W. Mak, Ph.D., D.Sc., M.D., F.R.S.2,4 Advanced Medical Discovery Institute, University Health Network Toronto, Canada Philippa C. Marrack, Ph.D.2 National Jewish Medical and Research Center and University of Colorado Health Sciences Center, HHMI Denver, Colorado Hugh O. McDevitt, M.D.2 Stanford University School of Medicine Stanford, California Ira Mellman, Ph.D.5 Yale University School of Medicine New Haven, Connecticut Malcolm A.S. Moore, D.Phil. Memorial Sloan-Kettering Cancer Center New York, New York Donald L. Morton, M.D. John Wayne Cancer Institute Santa Monica, California Lee Nadler, M.D. Dana-Farber Cancer Institute Boston, Massachusetts Stanley G. Nathenson, M.D.2,4 Albert Einstein College of Medicine Bronx, New York CANCER RESEARCH INSTITUTE Sir Gustav Nossal, M.D., Ph.D., F.R.S.2 The University of Melbourne Melbourne, Australia Victor Nussenzweig, M.D., Ph.D. New York University School of Medicine New York, New York Drew M. Pardoll, M.D., Ph.D.3,4 The Johns Hopkins University School of Medicine Baltimore, Maryland William E. Paul, M.D.2 National Institutes of Health Bethesda, Maryland Klaus Rajewsky, M.D.2,3 Harvard Medical School, The CBR Institute for Biomedical Research Boston, Massachusetts Anjana Rao, Ph.D.4 Harvard Medical School, The CBR Institute for Biomedical Research Boston, Massachusetts Jeffrey V. Ravetch, M.D., Ph.D. The Rockefeller University New York, New York Gert Riethmüller, M.D.3 University of Munich Munich, Germany Bijan Safai, M.D., D.Sc. New York Medical College Valhalla, New York Lawrence E. Samelson, M.D.4 National Cancer Institute Bethesda, Maryland Stuart F. Schlossman, M.D.2,3 Dana-Farber Cancer Institute Boston, Massachusetts Thomas A. Waldmann, M.D.2,3 National Cancer Institute Bethesda, Maryland Hans Schreiber, M.D., Ph.D.3,4 University of Chicago Chicago, Illinois David W. Weiss, Ph.D., D.Phil. The Hebrew UniversityHadassah Medical School Jerusalem, Israel Gregory W. Siskind, M.D. Weill Medical College of Cornell University New York, New York Pramod K. Srivastava, Ph.D.3 University of Connecticut School of Medicine Farmington, Connecticut Ursula B. Storb, M.D.4 University of Chicago Chicago, Illinois Zongtang Sun, M.D. Cancer Institute Chinese Academy of Medical Sciences Beijing, People's Republic of China Tomio Tada, M.D., D.M.S. Science University of Tokyo Research Institute for Biological Sciences Tokyo, Japan Toshitada Takahashi, M.D.3 Aichi Cancer Center Research Institute Nagoya, Japan Susumu Tonegawa, Ph.D.1,2 Massachusetts Institute of Technology Cambridge, Massachusetts Giorgio Trinchieri, M.D.3,4,5 Schering-Plough Laboratory of Immunological Research Dardilly, France Rolf M. Zinkernagel, M.D., Ph.D.1,2,3 University of Zurich Zurich, Switzerland Honorary Members Robert W. Baldwin, Ph.D., F.R.C. Path. University of Nottingham Nottingham, England Joseph H. Burchenal, M.D. (Retired) Memorial Sloan-Kettering Cancer Center New York, New York 39 Zoltan Ovary, M.D. New York University School of Medicine New York, New York Richmond T. Prehn, M.D.3 (Retired) University of Washington Seattle, Washington Bernard Roizman, Sc.D.2 University of Chicago Chicago, Illinois Otto Westphal, D.Sc., M.D. (Retired) Max Planck Institute for Immunobiology Freiburg, Germany Sir Michael Woodruff, M.D., F.R.S. (Retired) University of Edinburgh School of Medicine Edinburgh, Scotland Legend Isaac Djerassi, M.D. Mercy Catholic Medical Center Philadelphia, Pennsylvania 1 2 James F. Holland, M.D. Mount Sinai School of Medicine New York, New York 3 Henri Isliker, M.D. University of Lausanne School of Medicine Lausanne, Switzerland 5 George B. Mackaness, M.D., D.Phil., F.R.S. (Retired) Squibb Institute for Medical Research Princeton, New Jersey Georges Mathé, M.D. Institute of Oncology and Immunogenetics Villejuif, France 4 6 Nobel Laureate Member, National Academy of Sciences Member, Academy of Cancer Immunology Member, Fellowship Review Committee Member, Investigator Award and Predoctoral Program Review Committee Member, Grant Review Committee 40 BOARD OF TRUSTEES AND JUNIOR COUNCIL A passion for the cause and a grasp of practical realities are key traits shared by CRI’s Board of Trustees. Members apply skills honed in finance, communications, and other fields to ensure our sound fiscal operation and the success of fundraising and public-relations events. Their efforts are reinforced by the CRI Junior Council, made up of successful younger professionals dedicated to achieving annual fundraising goals. Board of Trustees Chairman of the Board Treasurer Ann W. Jackson Group President Time Inc. Women’s Group New York, New York Bruce D. Dixon Retired Partner Ernst & Young Greenwich, Connecticut Vice Chairmen of the Board Secretary Carter F. Bales Co-Managing Partner The Wicks Group of Companies, L.L.C. New York, New York Thomas G. Mendell Partner The Beacon Group, LP New York, New York Oliver R. Grace, Jr. President & CEO Anderson Group, Inc. Glen Head, New York Daniel L. Gray Chairman & CEO Northstar Companies, Inc. Lutherville, Maryland Thomas S. Johnson Chairman & CEO GreenPoint Financial Corp. New York, New York Trustees Edgar R. Berner Senior Advisor The Wicks Group of Companies, L.L.C.; Partner John Lang, Inc. New York, New York Carlos A. Ferrer Partner Ferrer Freeman & Company, LLC Greenwich, Connecticut Donald J. Gogel President & CEO Clayton, Dubilier & Rice, Inc. New York, New York Jacques C. Nordeman Chairman Nordeman Grimm, Inc. New York, New York Julian H. Robertson, Jr. Chairman Tiger Management LLC New York, New York President Patrick J. McGrath Pelham, New York Geoffrey O. Coley Managing Director Citigroup New York, New York Maurice J. Cunniffe Chairman & CEO AO Capital Corp. Greenwich, Connecticut Stuart P. Davidson Managing Director Labrador Ventures Palo Alto, California Richard M. DeMartini President, Asset Management Group Bank of America New York, New York Glenn J. DeSimone President & CEO Publicis Healthcare Communications Group International New York, New York William O. Grabe Partner General Atlantic Partners Greenwich, Connecticut Mrs. Stephen M. Kellen New York, New York Alexander P. Lynch Chairman, North American Mergers & Acquisitions Group J.P. Morgan Securities, Inc. New York, New York Lief D. Rosenblatt Senior Managing Member Satellite Asset Management, L.P. New York, New York Frank V. Sica Managing Partner Soros Private Funds Management LLC New York, New York Heidi Ueberroth Executive Vice President NBA Entertainment New York, NY Vance Van Dine Advisory Director Morgan Stanley Dean Witter & Co. New York, New York Honorary Trustees William E. Murray, Esq. Chairman Samuel Freeman Charitable Trust New York, New York Lloyd J. Old, M.D. Director Ludwig Institute for Cancer Research New York, New York Andrew M. Paul Chairman Enhanced Capital Partners LLC New York, New York Robert A. Posner Managing Director Commonwealth Holding, L.P. Brookline, Massachusetts Marjorie Atwood, Ph.D. Irvington, Virginia Howard P. Berkowitz Managing Partner BlackRock HPB Management New York, New York Roy J. Bostock Chairman and CEO B/com3, Inc. New York, New York The Honorable Bill Bradley Managing Director Allen & Company, Inc. New York, New York Donald G. Calder President G.L. Ohrstrom & Co., Inc. New York, New York Mrs. Richard B. Englund New York, New York CANCER RESEARCH INSTITUTE Wilbur H. Friedman, Esq. Partner Proskauer Rose LLP New York, New York Wayne T. Jervis, Jr. Los Angeles, California Mrs. Charles G. Gambrell Charlotte, North Carolina David B. Kinney Managing Partner Kinco Great Falls, Virginia Charles M. Grace Los Angeles, California David H. Shepard Coronado, California Mrs. Oliver R. Grace New York, New York Winthrop H. Smith, Jr. Chairman WHS Holding LLC Greenwich, Connecticut Junior Council Co-Chairs Leslie DeBauge New York, New York Lara S. Trafelet New York, New York Members Founder Skardon Baker Vice President JPMorgan Mergers & Acquisitions New York, New York Alan J. Hirschfield Wilson, Wyoming Helen Coley Nauts, D.Sc., Hon. 1907-2001 Julia Parker Benello San Francisco, California Arthur L. Jacobson Vice President - Investments SmithBarney Palm Desert, California Founding Chairman Kyle Clark Vice President, Human Resources Manager BBDO New York, New York Joyce Green Westhampton Beach, New York Oliver R. Grace 1909-1992 41 “When your family is hit by cancer, you realize how urgent this work is.” -Leslie DeBauge Leslie DeBauge is founder and Co-Chairman of CRI’s Junior Council, many of whose members have had their lives touched by cancer; “a proactive approach is critical for the long term,” she believes. She is a consultant on strategic planning and margin improvement for media and communications companies. John B. Fitzgibbons New York, New York Gregory R. Myers New York, New York Eric Rosen New York, New York Robin K. Stein Associate Broker Sotheby’s International Realty New York, New York Remy W. Trafelet Managing Partner Trafelet and Company New York, New York 42 FINANCIAL STATEMENTS Financial Statements for the Years ended June 30, 2003 and 2002 With Report of Independent Auditors To the Board of Trustees of Cancer Research Institute, Inc. We have audited the accompanying statements of financial position of Cancer Research Institute, Inc. (the “Institute”) as of June 30, 2003 and 2002, and the related statements of activities and cash flows for the years then ended. These financial statements are the responsibility of the Institute’s management. Our responsibility is to express an opinion on these financial statements based on our audits. We conducted our audits in accordance with auditing standards generally accepted in the United States. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement. An audit includes examining, on a test basis, evidence supporting the amounts and disclosures in the financial statements. An audit also includes assessing the accounting principles used and significant estimates made by management, as well as evaluating the overall financial statement presentation. We believe that our audits provide a reasonable basis for our opinion. In our opinion, the financial statements referred to above present fairly, in all material respects, the financial position of the Institute at June 30, 2003 and 2002, and the changes in its net assets and its cash flows for the years then ended in conformity with accounting principles generally accepted in the United States. August 28, 2003 CANCER RESEARCH INSTITUTE 43 Statements of Financial Position June 30 Assets Cash and cash equivalents Pledges receivable—net (Note 2) Other receivables Prepaid expenses Long-term investments, at fair value (Note 3) Office equipment and leasehold improvements—net of accumulated depreciation and amortization ($518,163 in 2003 and $481,285 in 2002) Total assets Liabilities and net assets Accounts payable and accrued expenses Grants and fellowships payable (Note 5) Deferred rent (Note 4) Total liabilities 2003 $ $ $ Net assets: Unrestricted: Board designated (Note 8) Other Total unrestricted Temporarily restricted (Note 7) Total net assets Total liabilities and net assets See accompanying notes. 10,616,649 $ 19,636,058 206,624 89,131 10,636,015 8,480,736 25,407,150 20,335 26,788 8,718,504 65,374 41,249,851 $ 94,848 42,748,361 180,638 $ 22,931,867 – 23,112,505 61,617 22,728,224 4,396 22,794,237 1,424,899 1,021,148 2,446,047 $ 2002 15,691,299 18,137,346 41,249,851 $ 1,236,432 351,275 1,587,707 18,366,417 19,954,124 42,748,361 44 CANCER RESEARCH INSTITUTE Statements of Activities Year ended June 30 Unrestricted Revenues, gains, reclassifications and other support Contributions: General, trustee, and related Combined federal campaigns Bequests/memorials Return on investments (Note 3) Special events: Income Direct costs Special events—net $ 3,813,375 $ 180,024 2,554,015 345,502 1,318,246 (289,485) 1,028,761 Designated contributions 2,000,848 Miscellaneous 57,996 Net assets released from restrictions (Note 7) 4,073,116 Total revenues, gains, reclassifications and other support 14,053,637 2003 Temporarily Restricted Total – $ 3,813,375 776,248 956,272 – 2,554,015 – 345,502 – – – Unrestricted $ 2,632,188 $ 401,726 2,136,820 (555,808) 1,318,246 (289,485) 1,028,761 1,264,749 (303,166) 961,583 2,622,598 57,996 3,660,923 67,105 (4,073,116) – 3,481,883 (2,675,118) 11,378,519 12,786,420 621,750 – 2002 Temporarily Restricted Total – $ 2,632,188 787,616 1,189,342 10,000 2,146,820 – (555,808) – – – 15,800,000 – (3,481,883) 13,115,733 1,264,749 (303,166) 961,583 19,460,923 67,105 – 25,902,153 Expenses (Note 9) Program: Science, medical and research information and communications 1,352,174 Research 10,470,822 Total program 11,822,996 – – – 1,352,174 10,470,822 11,822,996 1,439,883 11,193,074 12,632,957 – – – 1,439,883 11,193,074 12,632,957 Administration Marketing and development Total expenses – – – 623,491 748,810 13,195,297 593,768 868,329 14,095,054 – – – 593,768 868,329 14,095,054 Change in net assets Net assets, beginning of year Net assets, end of year See accompanying notes. 623,491 748,810 13,195,297 858,340 (2,675,118) (1,816,778) (1,308,634) 13,115,733 11,807,099 1,587,707 18,366,417 19,954,124 2,896,341 5,250,684 8,147,025 $ 2,446,047 $15,691,299 $18,137,346 $ 1,587,707 $18,366,417 $19,954,124 CANCER RESEARCH INSTITUTE 45 Statements of Cash flows Year ended June 30 Cash flows from operating activities Change in net assets Adjustments to reconcile change in net assets to net cash provided by (used in) operating activities: Depreciation and amortization Contributed investment securities Net realized and unrealized losses on investments Changes in operating assets and liabilities: Net decrease (increase) in pledges receivable, other receivables, and prepaid expenses Net increase (decrease) in accounts payable and accrued expenses, grants and fellowships payable, and deferred rent Net cash provided by (used in) operating activities Cash flows from investing activities Purchases of office equipment and leasehold improvements Net purchases of long-term investments Net cash used in investing activities Net increase (decrease) in cash and cash equivalents Cash and cash equivalents, beginning of year Cash and cash equivalents, end of year 2003 2002 $ (1,816,778) $11,807,099 36,878 (624,213) 138,745 25,779 – 887,167 5,522,460 (12,517,819) 318,268 3,575,360 (305,942) (103,716) (7,404) (1,432,043) (1,439,447) (73,194) (233,396) (306,590) 2,135,913 (410,306) 8,480,736 8,891,042 $10,616,649 $ 8,480,736 See accompanying notes. Notes to Financial Statements 1. Organization and Summary of Significant Accounting Policies Organization - The Cancer Research Institute, Inc. (the “Institute”) was founded in 1953 to foster the field of cancer immunology in the belief that the body’s immune system can be used to control and cure cancer. The Institute supports research with the immediate aim of increasing our understanding of the immune system and with the ultimate goal of developing immunological methods for the prevention and treatment of human cancer. The Institute also functions as a definitive source of public information on cancer immunology and cancer treatment. The Institute is a nonprofit corporation exempt from income tax under Section 501(c)(3) of the Internal Revenue Code. All contributions are considered to be available for unrestricted use unless specifically restricted by the donor. Net Assets - Temporarily restricted net assets are amounts that have been restricted in use by donor specification. The Institute has established a policy whereby donor-restricted contributions whose restrictions are met in the same reporting period are reported as unrestricted support. Cash Equivalents - Cash equivalents consist of money market funds with a maturity at the time they are acquired of no more than three months, except those held as part of the investment portfolio. Investments - Investments are measured at fair value in the accompanying statements of financial position. The following methods and assumptions were used by the Institute in estimating the fair value of its financial instruments: Cash and cash equivalents: The carrying amounts reported in the accompanying statements of financial position for cash and cash equivalents approximate fair value. Equities and debt securities: Fair values of equities and all debt securities are based on quoted market prices. Bequests - The Institute is a beneficiary under various wills and trust agreements, the total realizable amounts of which are not presently determinable. The Institute’s interest in bequests and trusts is recorded as revenue when it receives notice such interest has become unconditional. Office Equipment and Leasehold Improvements - Office equipment is depreciated over its estimated useful life using the straight-line method. Leasehold improvements are amortized over the term of the lease. Fellowships, Investigatorships and Grants - The Institute awards fellowships, investigatorships and grants covering periods of one to four years for the purpose of medical research. These awards are recorded as expenses at the time they become unconditional, which is usually when they are awarded. 46 CANCER RESEARCH INSTITUTE Science, Medical and Research Information and Communications Science, medical and research information and communications include costs primarily related to providing the public with information concerning cancer immunology, responding to inquiries from the public concerning cancer and communicating with applicants and awardees. Contributed Services - The Institute receives considerable contributed services. The fair value of contributed services provided by the Institute’s Scientific Advisory Council approximated $270,000 and $255,000 for the years ended June 30, 2003 and 2002, respectively, and has been recorded in the accompanying financial statements. Other contributed services have not been recognized as revenues and are not reported in the accompanying financial statements because they do not meet the criteria for recognition specified in Statement of Financial Accounting Standards No. 116, Accounting for Contributions Received and Contributions Made. Use of Estimates - The preparation of financial statements in conformity with accounting principles generally accepted in the United States requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, disclosure of contingent assets and liabilities at the date of the financial statements and the reported amounts of revenues and expenses during the reporting period. Actual results could differ from those estimates. The return on investments for the years ended June 30, 2003 and 2002 was as follows: Interest and dividends $ Net realized and unrealized losses $ 2003 484,247 $ (138,745) 345,502 $ 2002 331,359 (887,167) (555,808) 4. Commitments The Institute is obligated under a ten-year noncancelable lease for office space, expiring April 30, 2013, as follows: 2004 2005 2006 2007 2008 Thereafter Total $ 150,000 150,000 150,000 150,000 154,167 845,833 $ 1,600,000 Rent expense approximated $150,000 and $142,000 for the years ended June 30, 2003 and 2002, respectively. 5. Grants and Fellowships Payable 2. Pledges Receivable The Institute has pledges receivable as of June 30 as follows: As of June 30, 2003 and 2002, the Institute has unconditional grants and fellowships payable as follows: Due within one year Due between two and five years Total 2003 2002 $ 7,515,001 $ 7,666,168 13,567,440 19,754,829 21,082,441 27,420,997 2003 Due within one year $12,716,205 Due between two and five years 10,752,166 Total 23,468,371 Present value discount at a rate of 5% Pledges receivable—net (1,446,383) (2,013,847) $19,636,058 $25,407,150 Present value discount at rates of 3%-5% and 5%, respectively (536,504) (823,822) Grants and fellowships payable $22,931,867 $22,728,224 Approximately 94% and 95% of the Institute’s fiscal 2003 and 2002 pledges receivable, respectively, are due from a single donor. 3. Investments Investments, which management intends to hold for more than one year, are classified as long-term. The market values of longterm investments at June 30, 2003 and 2002 were as follows: Equity securities Fixed income Mutual funds Bonds U.S. Government obligations Mortgage-backed securities Cash equivalents and other Total long-term investments 2003 2002 $ 6,407,492 $ 4,384,150 3,765,015 – 130,564 1,104,636 – 921,835 106,763 726,436 – 978,129 226,181 603,318 $10,636,015 $ 8,718,504 2002 $11,253,128 12,298,918 23,552,046 6. Allocation of Joint Costs of Informational Materials In accordance with the AICPA’s Statement of Position 98-2, Accounting for Costs of Activities of Not-for-Profit Organizations and State and Local Government Entities that Include Fund Raising (“SOP 98-2”), the Institute incurred joint costs in the placement of advertisements aggregating $275,163 and $260,234 in fiscal 2003 and 2002, respectively. The Institute allocated such costs in accordance with SOP 98-2 as follows: June 30 Marketing and development $ Science, medical and research information and communication 2003 111,453 Administration Total 993 275,163 $ $ 162,717 2002 104,158 156,076 $ – 260,234 CANCER RESEARCH INSTITUTE 47 7. Temporarily Restricted Net Assets Temporarily restricted net assets as of June 30, 2003 and 2002 include the following amounts that are restricted for the following programs or activities by donor specifications: 2003 2002 Clinical and laboratory research $14,915,051 $17,578,801 Combined federal campaign restricted for future periods 776,248 787,616 $15,691,299 $18,366,417 Temporarily restricted net assets were released from restrictions in fiscal 2003 and 2002 in fulfillment of the following purposes: 2003 2002 $ 3,285,500 $ 2,552,573 787,616 929,310 $ 4,073,116 $ 3,481,883 Clinical and laboratory research Combined federal campaign restricted for future periods 8. Unrestricted Board Designated Net Assets Balances, June 30, 2001 $ Contributions Interest income Net realized and unrealized gains Clinical and laboratory research grants and fellowships Balances, June 30, 2002 Contributions Interest income Net realized and unrealized gains Clinical and laboratory research grants and fellowships Balances, June 30, 2003 $ Elaine R. Shepard Memorial Fund 231,578 $ – 15,952 267 – 247,797 – 15,545 34,254 – 297,596 $ John Hans Old and Roger E. Edna Alice Green Old Memorial Memorial Fund Fund 690,414 $ 45,509 $ – – 46,261 3,190 775 53 – – 737,450 48,752 – – 46,635 3,109 102,762 6,851 – (46,584) 886,847 $ 12,128 $ Gar Reichman Fund of Cancer Total Research Board Institute Designated 218,059 $ 1,185,560 69,775 69,775 14,357 79,760 242 1,337 (100,000) (100,000) 202,433 1,236,432 86,056 86,056 12,436 77,725 27,403 171,270 (100,000) (146,584) 228,328 $ 1,424,899 48 CANCER RESEARCH INSTITUTE 9. Functional Expenses Science, Medical and Research Marketing Information and Year ended June 30, 2002 Research and Communications Fellowship program $ 4,022,845 $ – Investigator Award program 1,000,000 – Predoctoral program 675,000 – Preclinical grants program 2,070,000 – Designated grants program 499,544 – Clinical trials program 2,203,433 – Salaries, benefits and related taxes – 568,806 Professional fees – 323,733 Printing, postage and supplies – 64,349 Rent – 47,123 Telephone – 4,736 Advertising – 162,717 Depreciation and amortization – 12,906 Miscellaneous – 167,804 2003 subtotals 10,470,822 1,352,174 Less special events – – 2003 totals $ 10,470,822 $ 1,352,174 Administration $ $ Special Development – $ – – – – – 366,002 73,557 68,282 47,447 4,471 993 12,906 49,833 623,491 – 623,491 $ – – – – – – 477,687 4,455 63,790 55,280 4,587 111,453 11,066 20,492 748,810 – 748,810 Events $ $ Total – $ 4,022,845 – 1,000,000 – 675,000 – 2,070,000 – 499,544 – 2,203,433 – 1,412,495 64,202 465,947 37,488 233,909 – 149,850 – 13,794 – 275,163 – 36,878 187,795 425,924 289,485 13,484,782 (289,485) (289,485) – $ 13,195,297 Science, Medical and Research Marketing Information and Year ended June 30, 2002 Research and Communications Fellowship program $ 3,147,382 $ – Investigator Award program 1,200,000 – Predoctoral program 1,800,000 – Preclinical grants program 1,450,000 – Designated grants program 476,715 – Clinical trials program 3,118,977 – Salaries, benefits and related taxes – 555,900 Professional fees – 280,421 Printing, postage and supplies – 69,907 Rent – 44,413 Telephone – 5,880 Advertising – 164,716 Depreciation and amortization – 9,022 Miscellaneous – 309,624 2002 subtotals 11,193,074 1,439,883 Less special events – – 2002 totals $ 11,193,074 $ 1,439,883 Administration $ $ – – – – – – 358,769 59,936 74,395 44,755 5,369 – 9,022 41,522 593,768 – 593,768 Special Development $ $ – – – – – – 519,265 46,682 52,816 53,046 5,369 140,139 7,735 43,277 868,329 – 868,329 Events $ $ Total – $ 3,147,382 – 1,200,000 – 1,800,000 – 1,450,000 – 476,715 – 3,118,977 – 1,433,934 61,511 448,550 40,088 237,206 – 142,214 – 16,618 – 304,855 – 25,779 201,567 595,990 303,166 14,398,220 (303,166) (303,166) – $ 14,095,054 10. Employee Benefit Plan Effective July 1, 1989, the Institute established a defined contribution retirement plan which provides for the Institute to make monthly contributions of at least 5% of the compensation of eligible employees. Eligible employees are those who have one year of service with the Institute. In addition, the Institute may contribute to the plan a discretionary amount equal to a percentage of compensation which is to be determined each plan year by the Institute. The plan allows the participants to make voluntary contributions up to limited amounts. During fiscal 2003 and 2002, the Institute contributed $92,395 and $80,674, respectively, to the plan. Discretionary contributions made by the Institute vest over a period of three years. © 2003 Cancer Research Institute Editor Lynne A. Harmer Writer Bill McCullam Designer Ian Plimsoll Printer Hu-tech Graphics, NYC PAST IS PROLOGUE Cancer Research Institute 681 Fifth Avenue, New York, NY 10022-4209 www.cancerresearch.org