Optimization of the CAR Affinity to Fine-Tune the CAR-T Cell Function

Abstract

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer treatment, especially for refractory or relapsed cancers that are resistant to conventional therapies. CAR-T cells are genetically engineered to express CAR molecules on their surface. These CAR-T cells are generated by th e introduction of CAR genes into T cells harvested from a cancer patient. Following the reinfusion of CAR-T cells into the patient, these cells recognize cancer cells by binding to cancer specific antigens to activate CAR signaling and eradicate the cancer cells. However, CAR-T cell therapies face challenges such as CAR-T cell exhaustion and severe toxicities, including on target, off tumor toxicity and cytokine release syndrome. To overcome these hurdles and enhance CAR-T cell performance, fine tuning CAR activation and exhaustion is essential. Optimizing the CAR affinity for its target antigen has proven to be effective to fine tune the CAR-T cell function. This review introduces CAR-T cell therapy, summarizes the current challenges, and explores ongoing efforts to optimize CAR functionality by adjusting the binding affinity.