How CAR T Cell Therapy is Pushing the Boundaries of Cancer Treatment

Adoptive cellular therapy is a branch of immunotherapy that channels the body’s cancer-fighting cells to eliminate the disease with minimal toxicity and the potential for lasting immune protection. Chimeric antigen receptor (CAR) T cell immunotherapy is a type of adoptive cellular therapy engineered to harnesses the immune system’s killer T cells to bind to the surface of cancer cells.

The ability to rationally engineer CAR T cells ex vivo to overcome the challenges posed by solid tumors really caught my interest and has rapidly become the major focal point of my research program.”

Paul Beavis, PhD, 2024 CRI Lloyd J. Old STAR

CAR T therapy has proven success against cancers like leukemia, lymphoma, and multiple myeloma. Two other types of adoptive cellular therapy, tumor-infiltrating lymphocyte (TIL) and T cell receptor (TCR) therapies, can only identify and destroy cancer cells that present antigens bound to major histocompatibility complex (MHC). The MHC protein molecule presents the antigen to T cells in a translatable form that can elicit an effective immune response. CAR T cells are genetically engineered to elicit immune response against tumor antigens and bypass the requirement of MHC proteins as is the case in other adoptive cellular therapies. 

Multiple CRI scientists are researching advances in this immunotherapy through unique therapeutic lenses, from how CAR molecules empower cell metabolism to influence their effectiveness to developing a new therapy with nanobody-based CAR T cells to target proteins in pancreatic tumors. Another investigative approach involves how stem cells might help produce a boundless source of off-the-shelf CAR T cells.  

CRI Lloyd J. Old STAR Paul Beavis, PhD, associate professor at both the Peter MacCallum Cancer Centre and University of Melbourne in Australia, is taking his CAR T therapy to a phase 1 clinical trial in 2025. Dr. Beavis said that while CAR T therapy has made transformational progress for some hematological malignancies, it has yet to make a significant impact on solid tumors. 

“Our major focus is to devise new strategies to enable CAR T cells to overcome the major hurdles to success in solid tumors: failure to persist, tumor-induced immunosuppression, tumor-antigen heterogeneity, and the challenge of trafficking to a solid tumor site,” he explained. Difficulties with solid tumors are well-known in the scientific community, since CAR T cells are only capable of recognizing antigens that express themselves on cell surfaces. 

One of the obstacles for CAR T therapy in solid tumors is their heterogeneity involving a large percentage of cancer cells that will either prove negative for the targeted antigen at baseline or following therapy. “Even with the highly successful CD19-targeted CAR T cells, relapse with CD19 negative tumor cells is observed,” Dr. Beavis elaborated. He uses sophisticated synergetic models to develop CAR T therapies that can effectively and safely activate localized anti-tumor immunity. 

CAR T therapy is an avenue of cancer immunotherapy that has produced highly impactful progress for cancer patients in recent years. Thanks to Dr. Beavis and other CRI scientists who diligently pursue additional advancements in this research area, we are ever closer to creating a world immune to cancer.