Concept CARs are picking up speed.

The field of adoptive T cell immunotherapy has been dominated by a chimeric antigen receptor (CAR) design that combines antigen recognition through antibody-derived domains and signaling into a single polypeptide. This conventional design redirects the immense cytotoxic potential of T cells toward tumors, and it is the core of several commercially marketed CAR-T cell products. Recent research in the field has been focused on developing more effective CAR designs, especially for solid tumors. Although most approaches have layered on top of the conventional CAR design, recent studies have taken a step back and redesigned the basic CAR to retain more of the natural structure of immunoreceptors such as the T cell receptor or killer immunoglobulin-like receptors. These redesigned CARs promote enhanced function in preclinical models compared with conventional CAR designs, including in the more challenging solid tumor setting, and several have entered the clinic with emerging data on their activity. These observations highlight the importance of considering CAR design and looking beyond conventional CARs when developing new T cell immunotherapy approaches.