DUARTE, Calif., October 31, 2011 — City of Hope received approval from the U.S. Food and Drug Administration (FDA) to conduct the first-ever study of an adoptive T cell therapy in patients undergoing autologous transplant for treatment of relapsed B cell lymphoma, the most common type of non-Hodgkin lymphoma. Stephen J. Forman, M.D., Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation (HCT) and chair of City of Hope’s Department of Hematology & HCT, and Michael Jensen, M.D., professor of pediatrics at the University of Washington in Seattle, lead the clinical research team that developed the immunotherapy, which uses genetically modified cells of a patient’s own immune system to treat the cancer.
An estimated 66,360 Americans will be diagnosed with non-Hodgkin’s lymphoma this year and more than 19,000 patients will die from the disease. Standard treatment of non-Hodgkin’s lymphoma can include chemotherapy, radiation and HCT, commonly referred to as a bone marrow transplant.
City of Hope is a pioneer in T cell immunotherapy research, helping to confirm the potential of genetically modified T cells as a treatment for cancer. The research team has identified numerous proteins as prime targets for the development of cancer immunotherapies, such as the CD19 protein that is present on B cell lymphoma cells. City of Hope is currently conducting a phase I clinical trial in brain tumor patients with a T cell therapy that targets the interleukin 13 receptor found on the surface of glioma cells.
“Our use of central memory T cells is unique to our therapy and sets our approach apart from other T cell treatments in development,” said Forman. “Central memory T cells have the potential to establish a persistent, lifelong immunity to help prevent recurrence of lymphoma after transplant."
Most lymphomas are cancers of the B lymphocytes, or white blood cells, which constitute a large part of the body’s immune system. The CD19 protein is present on the surface of malignant B cells, and serves as a key target for the T cells developed to treat lymphoma. Adoptive T cell therapies are created from healthy T cells obtained from the patient, which are then genetically modified to recognize a protein or receptor, such as the CD19 antigen, to target it specifically to cancer cells. The modified T cells are then cultured over a few weeks to increase their numbers to a level that can fight the cancer following reinfusion into the patient.
“In our clinical trial, patients receive the adoptive T cell therapy after they undergo a bone marrow transplant,” said Leslie Popplewell, M.D., clinical associate professor in City of Hope’s Department of Hematology & HCT, who serves as principal investigator for the clinical trial. “We want to evaluate whether this approach may provide a more conducive environment for healthy hematopoietic cells to engraft and allow the modified T cells to establish a reservoir of persistent memory cells to fight off lymphoma.”
In October, the phase I clinical trial began enrolling patients with high-risk intermediate grade B cell lymphomas to assess the safety and dosing of the therapy. Clinical trial participants will have their T cells harvested through blood collections, modified to recognize the CD19 protein and grown in culture while the patient then undergoes chemotherapy in preparation for a bone marrow transplant. After the autologous HCT in which the patient’s own healthy blood stem cells are reinfused, the genetically modified T cells also are infused and hopefully become part of an anti-cancer immune system that develops after transplant to help prevent recurrence of the lymphoma and improve the cure rate of the transplant.
