Clinical Trials Take CAR-T Therapy to Patients Who Need It

December 14, 2016 | by City of Hope

Stephen J. Forman Stephen J. Forman, M.D.

If a patient's immune system could be sufficiently bolstered, it could ultimately be a powerful weapon against blood cancers and other solid tumors. The trials at City of Hope are exploring the potential of an especially powerful type of immunotherapy that modifies T cells, then uses those cells to recognize a specific marker for cancer. That approach 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.

“Immunotherapy is clearly an area of tremendous potential for treating cancer,” said Stephen J. Forman, M.D., leader 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.”

City of Hope is also one of only a few cancer centers in the United States offering human studies in CAR-T cell therapy for brain tumors, and is the only cancer center investigating CAR-T cells administered directly to the brain tumor site and through the ventricular system.

Among the diseases that researchers are targeting with CAR-T cell therapy in current protocols are brain cancer, acute lymphoblastic leukemia, lymphoma and chronic lymphocytic leukemia. A new trial for acute myeloid leukemia (AML) is the first to target the CD123 antigen using CAR-T cells in AML patients. The trials use a similar approach tailored to each cancer: Patients have T cells collected from their blood, then modified using a lentivirus. The modified cells are then able to recognize proteins found on cancer cells — which, researchers say, triggers the immune system to fight the cancer.

City of Hope has the clinical and scientific expertise to house the entire process on its campus — including collecting the cells, manufacturing the lentivirus, modifying and replicating the cells, reinfusing them and caring for the patients here. 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,” said Forman, the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation. “That’s what we want to achieve for our cancer patients.”

Future T cell trials at City of Hope are opening the therapy to other types of cancers, including multiple myeloma, breast cancer and prostate cancer.

Investigators from the Hematologic Malignancies and Stem Cell Transplantation Institute working with CAR-T cells include Christine Brown, Ph.D., Heritage Provider Network Professor in Immunotherapy and associate director of the T Cell Therapeutics Research Laboratory; Elizabeth Budde, M.D., Ph.D., assistant professor; Myo Htut, M.D., assistant professor; Samer K. Khaled, M.D., assistant professor; Amrita Y. Krishnan, M.D., director of the Judy and Bernard Briskin Center for Multiple Myeloma Research and the Multiple Myeloma Program; Leslie Popplewell, M.D., associate clinical professor; Saul Priceman, Ph.D., assistant research professor; Tanya Siddiqi, M.D., assistant professor; Jamie Wagner, regulatory operations manager; and Xiuli Wang, M.D., Ph.D., associate research professor. Investigator for the brain tumor CAR-T clinical trial is Behnam Badie, M.D., chief of neurosurgery.
 

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