Beyond antigen dependence: Improving the therapeutic window of a signal 1 booster for adoptive cell therapy in solid tumors

CAR T cell therapy has transformed the treatment of several hematologic malignancies, yet comparable success in solid tumors remains elusive because of heterogeneous antigen expression, restricted T cell trafficking, and an immunosuppressive tumor microenvironment (TME) that limits T cell activation, expansion, persistence, and effector function.1,2 Insufficient access to tumor antigen can further limit signal 1 and compromise engineered T cell fitness. Pharmacologically inducible MyD88/CD40 signaling modules have been developed to provide controlled activation and enhance CAR T cell activity.