Mansilla-Soto Jorge, Milone Michael C
Departments of Immunology, Bioengineering, and BMT and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Mol Ther. 2025 Jun 4;33(6):2363-2367. doi: 10.1016/j.ymthe.2025.05.008. Epub 2025 May 8.
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.
过继性T细胞免疫疗法领域一直由嵌合抗原受体（CAR）设计主导，该设计通过抗体衍生结构域将抗原识别与信号传导整合到一条单一多肽中。这种传统设计将T细胞巨大的细胞毒性潜能重定向至肿瘤，并且它是几种商业销售的CAR-T细胞产品的核心。该领域最近的研究一直集中在开发更有效的CAR设计，尤其是针对实体瘤的设计。尽管大多数方法是在传统CAR设计的基础上进行改进，但最近的研究已退一步，重新设计了基本的CAR，以保留更多免疫受体（如T细胞受体或杀伤性免疫球蛋白样受体）的天然结构。与传统CAR设计相比，这些重新设计的CAR在临床前模型中促进了增强的功能，包括在更具挑战性的实体瘤环境中，并且有几种已进入临床，并有关于其活性的新数据。这些观察结果突出了在开发新的T细胞免疫疗法方法时考虑CAR设计并超越传统CAR的重要性。
