City of Hope has received approval from the U.S. Food and Drug Administration to conduct the first-ever study of an adoptive central memory T cell therapy in patients undergoing autologous transplant for treatment of relapsed B cell lymphoma, the most common type of non-Hodgkin lymphoma.

City of Hope’s Stephen Forman is combining central memory T cell therapy with hematopoietic cell transplantation. (Photo by AmyCantrell.com)

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 C. Jensen, M.D., professor of pediatrics at the University of Washington in Seattle, led the clinical research team that developed the immunotherapy, which uses genetically modified cells from a patient’s own immune system to treat the lymphoma.

T cells are a family of white blood cells that are critical to immune system function. City of Hope has contributed heavily to research into harnessing T cells against disease, helping to confirm the potential of genetically modified T cells as a treatment for cancer.

The research team has identified many proteins as prime targets for the development of cancer immunotherapies, and researchers currently are 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 as part of an autologous transplant 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.”

Stephen Forman, left, discusses ideas with Robert Seeger of Children’s Hospital Los Angeles at a ThinkCure event. (Keats Elliot Photography)

The new clinical trial focuses on the CD19 protein, which is found on B cell lymphoma. Because it is present on the lymphoma cells, the CD19 protein serves as a key target for T cells developed to treat lymphoma.

Adoptive T cell therapies are created from healthy T cells obtained from the patient. They are then genetically modified to recognize a protein or receptor, such as CD19, 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 after 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 and 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 and determine whether the cells can become part of the newly developing immune system after transplant.

Clinical trial participants have their T cells harvested through blood collection. The team modifies the T cells to recognize the CD19 protein and then grows those cells in culture while the patient undergoes chemotherapy in preparation for a bone marrow transplant. After the autologous transplant, in which the patient’s own healthy blood stem cells are reinfused, genetically modified T cells are also infused. Physicians hope these cells will become part of an anticancer immune system that develops after transplant to help prevent recurrence of the lymphoma and improve the cure rate of the transplant.