The California Institute for Regenerative Medicine (CIRM) has awarded City of Hope a $5.2 million grant to advance a new potential treatment for patients battling an aggressive form of brain cancer. 

T-cell therapies could enlist the immune system to destroy brain cancer. (Photo by Walter Urie)

Called adoptive T-cell therapy, the strategy seeks to direct the body’s immune system to fight cancer. Researchers modify genes in T cells so they recognize and attack cancer cells.

The grant from CIRM — California’s stem cell research agency — backs a project to harness what are called central memory T cells. Ordinarily, these specialized cells “remember” infectious agents such as viruses or bacteria long after someone recovers from a disease like the flu. If the virus or bacteria returns, central memory T cells quickly respond and boost the immune system to fight disease.

City of Hope researchers are modifying central memory T cells so they recognize glioma stem cells, the early cells that give rise to glioma, a challenging form of brain cancer. Glioma is hard to treat and often recurs, making prognosis poor. Glioma stem cells are highly resistant to chemotherapy and radiation, which enables them to survive and create new tumors despite treatment.

Stephen J. Forman, M.D., principal investigator on the study, explained that the team is engineering central memory T cells to recognize several proteins expressed by glioma stem cells.

“Central memory T cells have the potential to establish a persistent, lifelong immunity to help prevent brain tumors from recurring,” said Forman, the Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and director of the T Cell Immunotherapy Research Laboratory.

Christine Brown, Ph.D., associate research professor and co-principal investigator, noted that researchers are engineering the T cells to target a variety of proteins on glioma stem cells in hopes that no malignant cells will escape the treatment.

Researchers believe the project will lead to future studies targeting other cancers. The grant also will help them find the best way to deliver the treatment, create an efficient way to produce the therapeutic T cells and get approval for their use in a human clinical trial.

Michael Barish, Ph.D., chair of the Department of Neurosciences, and Behnam Badie, M.D., chief of the Division of Neurosurgery and director of the Brain Tumor Program, are co-investigators on the project.

The grant raises CIRM’s overall support for City of Hope to more than $49.7 million. The current grant comes from CIRM’s Early Translational Research Awards program, which supports early-stage projects aiming to identify drugs or cell types that could become disease therapies.