Download Jumonji may help explain how stem cells find cancer

R E S E A R C H
J U LY/AU G U ST 2015
A N D
T R E AT M E N T
U P D AT E S
800-COH-4DRS | cityofhope.org
I N THIS ISSUE
Jumonji may help explain how stem cells find cancer
Neural stem cells have a natural ability to seek out cancer cells in the brain. Recent
research from the laboratories of Michael Barish, Ph.D., and Karen Aboody, M.D., may
offer a new explanation for this attraction between stem cells and tumors.
Prior to joining City of Hope in 2003, Aboody, professor in the Department of Neurosciences
and the Division of Neurosurgery, found that neural stem cells are able to hone in on
invasive brain tumors. Since then, she and her colleagues have harnessed this ability to
target cancer cells in a clinical trial at City of Hope, delivering localized chemotherapy
directly to the most lethal form of brain cancer, high-grade gliomas. However, the specific
drivers behind the stem cells’ ability to find tumors remain elusive.
• Jumonji
• CAR T-cell immunotherapy
• Improving the quality of care
for bladder patients
• Clinical Trials at City of Hope
• New Faces of Hope
• Our locations
• Upcoming CME events
The latest study, led by Patrick Perrigue, a former graduate student mentored by Aboody
and Barish, points to a protein called Jumonji, expressed in both normal and cancer cells,
as a key factor.
Jumonji tweaks the process of gene expression, causing key genes to turn on or off. Some
of these genes are normally involved in immune activation, others in injury repair and
some in cellular aging. Tumor cells overproduce Jumonji, resulting in high production of
molecules involved in inflammation and recruitment of immune cells.
“There is a notion that cancer can be thought of as ‘wounds that do not heal,’” Barish said.
“Jumonji normally turns off during wound repair and regeneration, but in brain tumor cells
this does not appear to happen.” The bad news is that, left unchecked, these molecules
can help tumors develop and progress. The good news is that they also attract neural
stem cells and probably other therapeutic cells.
- Karen Aboody, M.D.
Now that the researchers have shed light on this process and the role of Jumonji, they can
begin searching for ways to manipulate the system to devise more effective therapies.
“We’ve opened up this little universe of possibility,” Barish said. “Jumonji influences many
cellular pathways, and we can use this information to develop new targeted therapies
and optimize existing ones.” He said future research may center on finding which specific
molecules neural stem cells use most when homing to tumors. They also may focus on
the glioma cells, targeting those molecules that boost tumor development or progression.
The prognosis for glioma is dismal — less than 10 percent of patients live five years or
longer — so every chance at improvement is welcome news.
Other scientists contributing to the study include Michael Silva (a former California
Institute for Regenerative Medicine-supported Bridges to Stem Cell Research trainee),
Charles Warden, Nathan Feng, Michael Reid, Daniel Mota, Lauren Joseph, Yangzi Isabel
Tian, Carlotta A. Glackin, Margarita Gutova and Joseph Najbauer.
– Michael Barish, Ph.D.
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New clinical trial harnesses the power of the
immune system to fight brain cancers
City of Hope initiates human study using CAR-T
cell immunotherapy to target glioblastomas
Already acknowledged pioneers in the use of immunotherapy,
City of Hope researchers are now testing another bold
approach to cancer treatment against one of medicine’s
biggest challenges: brain cancer. This month, we launched
a clinical trial using patients’ own modified T cells to fight
advanced brain tumors.
One of only a few centers in the United States offering
human studies in chimeric antigen receptor or CAR–T cell
therapy, City of Hope is the only center investigating CAR-T
cells which are injected directly into the brain tumor. In this
first-in-human study, patients with advanced brain tumors
will receive injections – directly at the tumor site – of immune
cells genetically modified to recognize certain markers on
cancer cells.
“The data from our preclinical studies makes us confident that
this treatment has the potential to be very powerful and last
longer than previous attempts at immunotherapy for brain
cancer,” said Behnam Badie, M.D., chief of neurosurgery at
City of Hope. “This could take the treatment of brain tumors
to the next level, and open up a new avenue of treatment to
patients who badly need it.”
The safety trial will evaluate the therapy in patients with
inoperable glioblastomas and advanced gliomas and in those
who have had their tumors surgically removed. The goal is to
determine a safe therapeutic dose.
City of Hope has been offering CAR-T cell immunotherapy in
clinical trials for patients with several types of blood cancers.
This current CAR-T trial extends the exciting therapeutic
approach to solid tumors, as well.
CAR-T cell therapy works by modifying a patient’s T cells to
recognize their own cancer cells. First, a sample of a patient’s T
cells are extracted, and then genetically modified to recognize
receptors on cancer cells. The modified T cells are able to
recognizing these cancer cells, and destroy them.
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This City of Hope trial will use a type of T cell known as memory
T cells, meaning they replicate in the body and “remember”
diseases they’ve fought previously. These memory cells give
rise to effective T cells that kill the cancer cells. The hope is
that the immune system will mount an attack on the existing
cancer – then do the same should the cancer recur.
The CAR-T cell laboratory is overseen by Christine Brown, Ph.D.,
associate director of the T Cell Therapeutics Research Laboratory,
and Stephen J. Forman, M.D., Francis & Kathleen McNamara
Distinguished Chair in Hematology and Hematopoietic Cell
Transplantation.
“CAR-T cell therapy has significant potential to fight not just
blood and bone marrow cancers, but a wide range of diseases
for which patients need better treatment,” Forman said. “City
of Hope is committed to maximizing the potential of this
revolutionary therapy for the sake of patients here and around
the world.”
For more information, visit clinicaltrials.coh.org and search
for IRB# 13384. The research is being funded through grants
from the California Institute of Regenerative Medicine and
the Gateway for Cancer Research Foundation. offer a new
explanation for this attraction between stem cells and tumors.
“CAR-T cell therapy has
significant potential to
fight not just blood and
bone marrow
cancers, but a wide
range of diseases for
which patients need
better treatment...”
A NATIONAL CANCER INSTITUTE-DESIGNATED COMPREHENSIVE CANCER CENTER
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Improving the quality of care for patients with
bladder cancer
The Institute of Medicine identified care coordination as a
key strategy with the potential to improve the safety and
effectiveness of care delivery. This is even more essential
with complex medical conditions like bladder cancer. At
City of Hope, we are leaders in the adoption of robotics
for urologic oncology. To date, we have performed over
8,300 urologic robotic surgical procedures, including
prostatectomy, nephrectomy and cystectomy.
Robotic cystectomy is a complex procedure which is often
performed on elderly patients with multiple co-morbidities.
Complication rates can be as high as 40 percent in the first
three months postoperatively. We identified the key aims
of the Institute of Medicine directive for the future of health
care and incorporated these into a care coordination model
for our cystectomy patients.
City of Hope began by assessing the length of stay,
readmission rate, top reasons for readmission and utilization
of services and resources for our cystectomy patients. We
convened a multidisciplinary team consisting of a urologist,
medical oncologist, social worker, case manager and
supportive care medicine physician in order to develop a
care pathway and improve upon these metrics.
The care pathway begins with the identification of a newly
diagnosed bladder cancer patient. Preoperative assessment
and care planning are performed with the patient and family,
including identification of any biopsychosocial barriers to
care on an electronic screening platform. Patients and family
members undergo extensive preoperative education on the
specifics of treatment. Discharge planning begins prior to
admission. Evidenced-based guidelines and standardized
order sets are used to guide care during the hospitalization.
Patients and families are screened for postdischarge
barriers to care, contacted by phone within 24 hours of
discharge and have close follow up in the clinic over the
next four weeks. Quality metrics, including length of stay,
readmission causes and rates, adherence to pathway and
postoperative complications, are regularly tracked.
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Since April 2014, 55 patients have undergone robotic
cystectomy on this pathway. Results to date have
demonstrated a decrease in length of stay and readmissions
for dehydration, with an increase in advanced directives on file
and an improvement in coordination of care and transitions
to home. We believe this pilot program is improving the
quality of care being delivered to our patients and is a model
for incorporating the aims of the Institute of Medicine to
move us forward in the future of health care reform.
“Patients and family
members undergo
extensive preoperative
education on the
specifics of treatment.
Discharge planning
begins prior to
admission...
We believe this pilot
program is improving
the quality of care
being delivered to
our patients...”
PHYSICIANews
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800-COH-4DRS | cityofhope.org
Profiles of clinical trials currently underway at
City of Hope
IRB# 13351 (Tanya Siddiqi)
Title: Phase I Study to Evaluate Cellular Immunotherapy Using Central Memory-Enriched T Cells Lentivirally
Transduced to Express a CD19-Specific, Hinge-Optimized, CD28-Costimulatory Chimeric Receptor
and a Truncated EGFR Following Lymphodepleting Chemotherapy in Adult Patients with CD19+ B Cell
Lymphoproliferative Neoplasms
IRB# 14352 (Anthony Stein)
Title: A Phase I, Multicenter, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, Pharmacodynamic, and
Clinical Activity Study of Orally Administered AG-221 in Subjects with Advanced Hematologic Malignancies
with an IDH2 Mutation
IRB# 12267 (Amrita Krishnan)
Title: Phase I/II Trial of MLN9708 plus Pomalidomide and Dexamethasone for Relapsed or Relapsed
Refractory Multiple Myeloma
IRB# 13401 (Jana Portnow)
Title: A Phase I Study of Cytosine Deaminase-Expressing Neural Stem Cells in Combination with Oral
5-Fluorocytosine and Leucovorin for the Treatment of Recurrent High-Grade Gliomas
IRB# 13355 (Marwan Fakih)
Title: A Phase I Clinical Trial of MEK162 in Combination with FOLFOX in Patients with Advanced Metastatic
Colorectal Cancer Who Failed Prior Standard Therapy
IRB# 14099 (Joanne Mortimer)
Title: A Pilot Study of 64Cu-DOTA-Trastuzumab Positron Emission Tomography in Treatment of Advanced
HER2 Positive Breast Cancer with the Antibody Drug Conjugate Ado-Trastuzumab Emtansine
There are more than 200 therapeutic clinical trials currently ongoing at City of Hope. Profiled
above are a few trials currently underway. For more information on a specific clinical trial, please
call 626-218-1133. For a full listing of clinical trials, visit clinicaltrials.coh.org.
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A NATIONAL CANCER INSTITUTE-DESIGNATED COMPREHENSIVE CANCER CENTER
PHYSICIANews
800-COH-4DRS | cityofhope.org
New Faces of Hope
City of Hope recently welcomed the following new physicians to its medical staff:
Alex Herrera, M.D.,
Assistant Professor,
Hematology/HCT
Location: Duarte
Monzr Al Malki, M.D.,
Assistant Clinical Professor,
Hematology/HCT
Location: Duarte
Yanghee Woo, M.D.,
Associate Clinical Professor,
Director, Gastroenterology
Minimally Invasive Therapy
Location: Duarte
Ali Zhumkhawala, M.D.,
Assistant Clinical Professor,
Urology and Urologic Oncology
Location: Duarte
Please call 800-COH-4DRS to reach any City of Hope physician.
Our Locations
City of Hope’s community practices extend the institution’s reach to more patients by bringing premier care to local
communities in central and northern Los Angeles and Riverside counties.
MAIN CAMPUS
Duarte
1500 E. Duarte Road
Duarte, CA 91010
COMMUNITY LOCATIONS
Antelope Valley
44151 15th St. West
Lancaster, CA 93534
Arcadia
301 W. Huntington Drive, Suite 400
Arcadia, CA 91007
Corona
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Corona, CA 92879
Glendora
210 S. Grand Ave., Suite 425
Glendora, CA 91741
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Mission Hills
15031 Rinaldi St., Suite 150
Mission Hills, CA 91345
Palm Springs
1180 No. Indian Canyon Drive, Suite #E-218
Palm Springs, CA 92262
Pasadena
630 S. Raymond Ave., Suite 220
Pasadena, CA 91105
Rancho Cucamonga
8283 Grove Ave., Suite 207
Rancho Cucamonga, CA 91730
Santa Clarita
23861 McBean Parkway, Suite B14
Santa Clarita, CA 91355
Simi Valley
1157 Swallow Lane
Simi Valley, CA 93065
South Pasadena
209 Fair Oaks Ave.
South Pasadena, CA 91030
West Covina
1250 S. Sunset Ave., Suite 303
West Covina, CA 91790
To refer a patient, call
800-COH-4DRS, or visit
cityofhope.org/refer-a-patient.
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CME CORNER – Upcoming events
Neoplastic Hematopathology Update:
Lymphoma Symposium
Visit cityofhope.org/cme to register and learn more about
other CME opportunities, including:
When:
Where:
• E-learning library offers a portfolio of courses FREE OF CHARGE.
Credits:
Sat., Sept. 19, 2015, 7:30 a.m. to 4:30 p.m.
Westin Pasadena
191 N. Los Robles Ave, Pasadena, CA
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American Board of Pathology SAMs credit eligible
Multidisciplinary Approaches to Cancer Conference
When:
Where:
Credits:
Thurs., Nov. 5-8, 2015
Wynn Encore Las Vegas
3131 Las Vegas Blvd, Las Vegas NV
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• Grand Rounds: Members of City of Hope’s medical staff can speak on topics
ranging from cancer to other life-threatening diseases.
To contact the CME office directly, call 800-826-HOPE (4673), ext. 65622,
or email [email protected].