City of Hope researchers unlock the potential of the immune system to fight cancer

November 23, 2014
Physicians and scientists at the Hematologic Malignancies and Stem Cell Transplantation Institute are using T cell therapy against blood cancers and other diseases
DUARTE, Calif. — If a patient’s immune system could be sufficiently bolstered, it could ultimately be a powerful weapon against blood cancers and other diseases. That approach, known widely as immunotherapy, is much more than a narrow field of study at City of Hope. It’s the central component of a host of promising clinical trials now underway.
The trials at City of Hope are exploring the potential of an especially powerful type of immunotherapy that modifies white blood cells known as T cells, then uses those cells to recognize a specific marker for cancer. City of Hope is one of only seven centers nationwide studying this therapy – and the only one in California offering clinical trials.
City of Hope is now using this approach – known as chimeric antigen receptor, or CAR – T cell therapy   in clinical trials for leukemia, lymphoma and other hematologic malignancies. The trials use a similar approach tailored to each cancer: Patients have their T cells collected from the blood then modified using a lentivirus – a specific type of virus that encodes the T cells with specific antigen receptors. The modified cells are then able to recognize proteins found on cancer cells – which, researchers say, triggers the immune system to fight the cancer.
“Immunotherapy is clearly an area of tremendous potential for treating cancer,” said Stephen J. Forman, M.D., chairman of the Hematologic Malignancies and Stem Cell Transplantation Institute and director of the T Cell Immunotherapy Research Laboratory at City of Hope. “We’re proud and excited to be among the few teams in the country working on this type of immunotherapy and to have the opportunity to offer these therapies to our patients through clinical trials.”
Among the diseases that City of Hope researchers are targeting with CAR T-cell therapy in current protocols are lymphoma, acute lymphoblastic leukemia, and chronic lymphocytic leukemia. A trial for acute myeloid leukemia will be the first ever to target the CD123 antigen – a molecule that helps signal a protein important to the immune system – using CAR T cells in AML patients.  
Several centers nationwide are working with CAR T cell therapies, each taking slightly different approach and studying different cancers and different targets.
City of Hope has the clinical and scientific expertise to house the entire process on it s campus – including collecting the cells, manufacturing the lentivirus, modifying and replicating the cells, and re-infusing them. Researchers have focused on enriching the memory of T cells, with the aim of creating cells that will be long-lived in the body and reproduce. This is what could allow for the T cell therapy approach to potentially have a longer-lasting effect than medications, which would have to be taken repeatedly.
“When you get a cold or infection, the immune cells specifically track down and rid the body of infected cells,” Forman said. “That’s what we want to achieve for our cancer patients.”
Cancers are frequently able to develop properties that trick the immune system into believing that they are part of the body itself, and researchers believe the modified T cells will be able to recognize cancer cells and signal the immune system to fight.
Future T cell trials at City of Hope will open the therapy to other types of cancers, including brain cancer, multiple myeloma and breast metastases to the brain.
Investigators from the Hematologic Malignancies and Stem Cell Transplantation Institute working with CAR T cells include Elizabeth Budde, M.D., Ph.D., assistant professor; Christine Brown, Ph.D., associate director of the T Cell Therapeutics Research Laboratory; Myo Htut, M.D., assistant professor; Samer K. Khaled, M.D., assistant professor; Amrita Y. Krishnan, M.D., F.A.C.P., director of the Multiple Myeloma Program; and Leslie Popplewell, M.D., F.A.C.P., associate clinical professor; Saul Priceman, Ph.D., assistant research professor; Tanya Siddiqi, M.D., assistant professor; Jamie Wagner, senior research associate in Cancer Immunotherapies and Tumor Immunology; and Xiuli Wang, assistant research scientist in Cancer Therapies and Tumor Immunology.
Nicole White
About City of Hope
City of Hope is a leading research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as a comprehensive cancer center, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the nation. City of Hope’s main hospital is located in Duarte, Calif., just northeast of Los Angeles, with community clinics in southern California. It is ranked as one of "America's Best Hospitals" in cancer by U.S.News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation and genetics.