Chimeric antigen receptor (CAR)-mediated therapy may slow down or even stop metastasis in several types of solid tumors, researchers at The University of Texas MD Anderson Cancer Center discovered in preclinical experiments.

A novel approach called CAR-T cell therapy (cell-based immunotherapy) works by recruiting T cells that have been genetically modified to express specific immune-regulatory factors in their blood. The engineered T cells, called chimeric antigen receptor (CAR)-mediated-based-adaptive T cells, are able to immunize against specific tumor antigens, which are expressed at high levels by cancer cells. Despite these approaches being FDA-approved, advanced-phase clinical trials involving these CAR-T cells have been hindered by the difficulty of matching high tumor dosage with sufficient tumor-specific T cell immunotherapy that can effectively eradicate cancer cells that have acquired resistance to the CAR-T cell therapy.

A research team led by Dr. William B. Scott, Ph.D., an associate member of the Cancer Metabolism and Signaling Networks Institute at MD Anderson, reported that CAR-mediated immunotherapy was able to overcome this limitation by utilizing an RNA-binding protein (RBP5) in the mice that are naturally resistant to CAR-T cell therapy. RBP5 is known to bind to an antigenic protein, a “signaling receptor” that acts as a gatekeeper of communication between cells. When CAR-T cells were used in this manner, the researchers discovered that the RBP5 inhibitor failed to elicit robust anti-tumor immune responses in the treated mice. These findings are published in the online March 25 issue of Cancer Discovery and offer a solution for addressing a serious obstacle to effective CAR-T cell therapy, namely the relatively poor signal-transmitting performance of the CAR-T cells in patients.

A major hurdle in developing CAR-T cell therapy for T cell-positive cancer is that it lacks the DNA damaging property of conventional CAR-T cells. This weakens the immunotherapy’s ability to target tumor-specific cell populations and makes it less effective in combination with the conventional immunotherapies used in the clinic.