Cancer Researcher Thomas Martin Receives $4.6 million CIRM Grant

UC San Francisco’s Thomas G. Martin, MD, a leading expert in blood cancers, has received a grant of nearly $4.6 million from the California Institute of Regenerative Medicine (CIRM) to produce a CAR T cell therapy for multiple myeloma, the second most common malignancy among blood cancers.

The research project, “A 1XX-enhanced and fully non-viral BCMA CAR T cell therapy for Relapsed and Refractory Multiple Myeloma (UCCT-BCMA-1),” will enable Martin and his team to engineer T cells to target and kill B cell maturation antigen+ (BCMA+) myeloma cells to treat relapsed and refractory multiple myeloma (RRMM).

Multiple myeloma is a cancer that forms in plasma cells, a type of white blood cell. In multiple myeloma, the body produces too many plasma or myeloma cells. These cells produce antibodies that the body does not need, which can form tumors and cause other problems, such as bone fractures and kidney failure. Currently, there are no lasting treatments for RRMM and only about 30% of patients can access current BCMA chimeric antigen receptor (CAR) T therapies. Even with new treatments, patients usually relapse and exhaust all treatment options.

CAR T-cell therapy uses the patient's own immune cells to attack cancer cells. Martin’s late-stage preclinical study will use genome editing to produce cryopreserved autologous TRAC locus 1XX BCMA CAR T cells to improve the safety and efficacy of treatment.

“We will incorporate innovations in CAR T cell design and CRISPR-mediated transgene insertion to generate an improved BCMA CAR T cell therapy, enhancing safety, purity, potency and persistence,” said Martin, a UCSF professor of Medicine and associate director of UCSF's myeloma program. “This therapy will be made available to diverse California patients who lack access to current FDA-approved therapies.”

The project was one of three clinical-stage research projects recently funded by CIRM to advance stem cell and gene therapy treatments for a variety of conditions ranging from neurodegenerative diseases to blood cancers. The award will support all stages of clinical trial development with the objective being a phase 1 clinical trial.

“While there are currently two FDA approved anti-BCMA CAR T therapies, these both require integration of lentiviruses to create CAR T cells and therefore have associated risks, constraints and access issues that are likely to be less with genome editing of CAR T cells,” said AJ Chari, MD, director of the UCSF Multiple Myeloma Program.

Martin is also clinical research director of hematologic malignancies (blood cancers) at the UCSF Helen Diller Family Comprehensive Cancer Center and co-leader of the center’s Cancer Immunology & Immunotherapy Program.