A biomimetic five-module chimeric antigen receptor ( <sup>5M</sup> CAR) designed to target and eliminate antigen-specific T cells
Shio Kobayashi, Martin A. Thelin, Heather L. Parrish, Neha Deshpande, Mark S. Lee, Alborz Karimzadeh, Monika A. Niewczas, Thomas Serwold, Michael S. Kuhns
Abstract
Significance T cells are driven by five-module receptor complexes composed of a T cell receptor (TCR) module, three CD3 signaling modules, and a coreceptor module. We adapted this architecture to engineer a biomimetic five-module chimeric antigen receptor ( 5M CAR) that consists of a chimeric receptor module, composed of the antigen recognized by pathogenic T cells fused to elements of the TCR that facilitate assembly with the three CD3 modules, and a surrogate coreceptor module that enhances signaling. We show that cytotoxic T lymphocytes expressing 5M CARs can rapidly eliminate pathogenic T cells and prevent them from mediating autoimmune disease in mice. Overall, this work describes a CAR platform and its use in mitigating T cell-mediated pathologies.