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701 Grove Road Greenville, SC 29605 Philanthropic Opportunity Pediatric Leukemia Research Opportunity Although our society enjoys great advances in medical technology, we still have much to learn. Even today, many children with chronic, life-threatening illnesses are not promised cures. This paper will review the current protocol of treatment for pediatric leukemia, examine other innovative ways of treating cancer in general, suggest an alternative to the current treatment for pediatric leukemia, and request your further involvement as a philanthropic partner. At Greenville Hospital System, the Oncology Research Institute (ORI) and Children’s Hospital have launched an initiative that seeks to produce a superior success rate for treatment of pediatric leukemia that simultaneously alleviates much of its pain and side effects. In addition, ORI hopes to conduct further research initiatives for children with other life-threatening, cancer-related conditions. Treating Pediatric Leukemia Today Standard treatment for pediatric leukemia generally involves high-dose chemotherapy and bone marrow transplantation (BMT). When bone marrow transplantation was first proposed, research indicated the physician should give sufficiently high doses of chemotherapy to destroy all tumor cells, while also destroying most of the patient’s other blood cells and immune system. The physician would then rebuild the lost immune system through a bone marrow transplant from a matched donor. BMT requires a donor whose tissue match is close to the recipient’s own tissue. Therefore, an identical twin was assumed to be ideal. However, when an identical twin was the donor, the therapy failed. This unexpected turn changed researchers’ understanding of this therapy. Apparently, high-dose chemotherapy did not annihilate the cancer cells in this therapy. Instead, such an outcome was the effect of the slightly foreign immune cells from the donor— not the perfectly matched twin donors. These results have prompted the hospital system to research other alternatives to combat this disease. In 1998, the hospital system recruited Thomas Wagner, Ph.D., and his associates, three senior scientists from Ohio University, to research other treatments that have yielded positive results. The ORI program is comprised of three laboratories: cell, molecular, and developmental biology. Scientists at ORI are attempting to use new knowledge of the detailed molecular pathways navigated by tenacious cancer cells along with others utilized by the body’s immune system that counteract their persistence to develop new cancer therapies. Because of their specificity and selectivity, these potential new therapies hold the promise of providing an effective means of treating cancer with few side effects. 1 Successes Treating Cancer One of the most promising ORI clinical trials is Cellular Tumor Vaccine Therapy. This therapy, now in Phase II clinical trials, has proven effective in some patients with melanoma and renal cell carcinoma. This vaccine is effective because it presents the tumor’s “signature” to T cells (a subpopulation of white blood cells of the patient’s immune system), stimulating them to generate “killer” T cells called Cytotoxic T Lymphocytes (CTLs), which can attack and destroy tumor cells wherever they might be situated within the body. Because the surprising results from identical twin donors suggest that the truly curative aspect of present therapy is immunological, both ORI and the Children’s Hospital are attempting to apply a modification of ORI’s successful “vaccine” immunotherapy to pediatric leukemia. This CTL treatment, unlike the current treatment for pediatric leukemia, does not require high doses of chemotherapy. With one simple infusion, it gives the child a less painful treatment alternative to destroy tumor cells. Research Proposal Benefits Through a cooperative program in children’s cancer research, the GHS Children’s Hospital and ORI hope to discover an immune therapy treatment for pediatric leukemia that is less painful and more successful than are current treatments. The Challenge ORI and its Basic Research Program are equipped with the latest instruments and facilities for state-of-the-art cancer research. Its three divisions are guided by outstanding, visionary senior medical researchers. Unfortunately, supporting staff and medical research associates are limited, which restricts the number of research projects that can be undertaken and, subsequently, the number of cancers for which new therapy can be developed. A generous gift from B.K. and Frances Bryan seeks to address these limitations. Their gift has initiated The New Hope Fund, which will house both an endowment and funds for immediate use. The New Hope Fund will support new therapy team efforts to research specific cancer cures, the first of which will be pediatric leukemia. Funds generated will provide stipends for 1) research associates committed to curing pediatric leukemia and other targeted cancers and (2) the costly supplies and equipment required for their work. The GHS Office of Philanthropy & Partnership is seeking people who wish to be Visionary Philanthropists with the hospital system in this project. The New Hope Fund is visionary. Funds will be used for innovative research directed toward a more effective and less painful treatment. This project provides an opportunity for compassionate and bold philanthropists to be added to this quest to benefit those in need within the greater Greenville community, as well as throughout the world. 2 Our Approach Because our first patient group involves children with a significantly impaired immune system, the ORI plans to simulate steps in an immune response to a vaccine in the laboratory rather than within the patient. Once CTLs have been generated in the laboratory, they will re-introduce billions of these “killer” T cells into the patient by intravenous infusion. In turn, it is hoped that this reintroduction will generate an immune response against leukemia cells. Since this approach is significantly different from ORI’s present vaccine therapy, the institute must first confirm the soundness of this approach by way of animal studies. In these studies, research associates at GHS and ORI will fuse mouse leukemia cells with mouse dendritic cells. This process will generate mouse dendritomas to present the tumor “signature” of the leukemia cells to mouse T cells. Mouse T cells will be removed from the experimental mice and incubated with these dendritoma “vaccine” cells in a culture in ORI’s Cell Biology laboratory. The CTLs against leukemia so generated will be expanded for several weeks. These laboratory generated, anti-leukemia CTLs will be infused back into mice that have been seeded with high levels of leukemia to mimic children with advanced leukemia. This step will help determine if the therapy can effectively eliminate disease cells. If these experiments indicate such therapy to be effective, the ORI will then apply to the FDA to initiate a Phase I clinical trial to test children who have failed standard therapy. If these initial trials and follow-up Phase II trials prove successful, the ORI and Children’s Hospital may then begin applying this less devastating approach to the initial treatment of childhood leukemia. Our Results Dr. Wagner and his colleagues have been extremely successful at Greenville Hospital System, having filed 20 patents and having completed the first Phase I clinical trial developed solely in South Carolina. The hospital system is also one of a few targeted drug development sites designated by the National Cancer Institute in the Southeast sponsoring early phase clinical trials. The ORI team is currently investigating and developing novel therapies for melanoma, breast, renal cell, and prostate cancers. Request for Support Mouse studies have already been initiated in the ORI to test this hypothesis. We hope to have supporting data in the coming months that will document success in the lab. However, this venture cannot be possible without the support of additional community Visionary Philanthropists. The New Hope Fund presents a visionary revenue pool that creates exploratory research opportunities to find cures for today’s illnesses. To be successful, however, it needs the commitment of a core group of philanthropists who will provide their financial support to this effort. In all, this collaborative project, to be known as the New Hope Fund for Pediatric Leukemia Research, requires a total of $1.3 million, over a five-year period. The fund needs up to 13 philanthropists who will commit to a gift in the range of $20,000-$25,000 per annum for 3 five years. Because of your considered support in this vision, children in Greenville with Leukemia will have access to a treatment option more effective and less painful years before the rest of the world. Closing As you consider your gift, keep in mind the plight of children who have cancer. Can we stop the pain that current treatments inflict? As community leaders and philanthropists, will you do all you can to support new and innovative research to help all our children lead better lives? Cancer treatments are being developed in Greenville that have the potential to benefit generations to come throughout the entire world. Appendix Initial Budget Year 1 ..........................................................$530,000 Year 2 ..........................................................$130,000 Year 3 ..........................................................$205,000 Year 4 ..........................................................$205,000 Year 5 ..........................................................$205,000 Total for project .......................................$1,275,000 Year 1 and 2 expenses cover the salary/benefits and supplies of two medical research associates to perform the initial mouse studies required. In addition, year one expenses include the purchase of Cell Sorter required in meeting FDA regulations for this work. As we approach Year 3, we will need a part-time medical director to oversee patient treatment initiatives. At the three-year mark, we expect to have 10 to 15 patients enrolled in Phase I clinical trials. These trials will evolve into Phase II trials that will evoke interest and financial support through application to the National Cancer Institute (NCI), foundations, and other granting agencies to bring this treatment approach to market. 4