Abstract Chimeric antigen receptor (CAR) T cell therapy has become an indispensable immunotherapy for the treatment of some hematologic cancers, but still faces numerous challenges in the form of antigen escape, variable patient responses, toxicities, limited CAR T cell persistence, and high cost, particularly against solid tumors. This Review discusses the potential role of the endogenous T cell receptor (TCR) as either a hindrance or partner to CAR T cell function.
