Enhanced Chimeric Antigen Receptor T Cell Therapy through Co-Application of Synergistic Combination Partners

Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable response rates and revolutionized the treatment of patients suffering from defined hematological malignancies. However, many patients still do not respond to this therapy or relapse after an initial remission, underscoring the need for improved efficacy. Insufficient in vivo activity, persistence, trafficking, and tumor infiltration of CAR T cells, as well as antigen escape and treatment-associated adverse events, limit the therapeutic success. Multiple strategies and approaches have been investigated to further improve CAR T cell therapy. Besides genetic modification of the CAR itself, the combination with other treatment modalities has the potential to improve this approach. In particular, combining CAR T cells with clinically approved compounds such as monoclonal antibodies and small molecule inhibitors might be a promising strategy. Combination partners could already be applied during the production process to influence the cellular composition and immunophenotype of the final CAR T cell product. Alternatively, simultaneous administration of clinically approved compounds with CAR T cells would be another feasible avenue. In this review, we will discuss current strategies to combine CAR T cells with compounds to overcome recent limitations and further enhance this promising cancer therapy, potentially broadening its application beyond hematology.