Recent progress in improving the safety and efficacy of chimeric antigen receptor T cell therapy

Chimeric antigen receptor (CAR) T cell therapy has demonstrated unprecedented feat in a variety of malignancies, providing a transformative approach to treating patients with hematological malignancies and solid tumors. Although CAR-T cell therapy has shown remarkable anti-tumor activity, toxicities and tumor antigen escape have largely compromised its efficacy. In the case of solid-tumor management, it has shown modest results to date, likely due to heterogeneous antigen expression, an inhibitory tumor microenvironment, and other immunosuppressive factors. The predominant goal for this field now is to achieve more precise tumor recognition and design CARs with more robust proliferative ability. To this end, a multitude of novel CARs and new immunomodulatory antibodies are being developed and tested clinically. Intense efforts are underway to improve the engineering of synthetic immunotherapies and combine these strategies with other agents to amplify immune responses. In this review, we will discuss the current landscape of CAR-T cell therapy, with an emphasis on primary challenges that need to be addressed urgently. In addition, we characterize some newly designed CARs proposed for improving specificity and proliferation of CAR-T cells, offering new insights into improving safety and efficacy of CAR-T cell therapy.