Engineering Robust T Cells for Cancer Immunotherapy

The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has demonstrated remarkable clinical efficacy in the treatment of advanced cancers, particularly B-cell malignancies. However, challenges including imperfect specificity, antigen escape, and tumor-mediated immunosuppression limit the safety and long-term efficacy of adoptive T-cell therapy. Here, I will highlight the development of next-generation T cells that can target multiple cancer antigens and resist immunosuppression, thereby increasing the robustness of therapeutic T cells against tumor defense mechanisms. In particular, this presentation will focus on the development of rationally designed cytotoxic molecules that enable T cells to interrogate intracellular oncoproteins prior to triggering target-cell apoptosis, resulting in a two-step verification system that increases targeting specificity against tumor cells.