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The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity.

Christopher W Helsen | Joanne A Hammill | Vivian W C Lau | Kenneth A Mwawasi | Arya Afsahi | Ksenia Bezverbnaya | Lisa Newhook | Danielle L Hayes | Craig Aarts | Bojana Bojovic | Galina F Denisova | Jacek M Kwiecien | Ian Brain | Heather Derocher | Katy Milne | Brad H Nelson | Jonathan L Bramson
Nature communications | 2018

Engineering T cells with chimeric antigen receptors (CARs) is an effective method for directing T cells to attack tumors, but may cause adverse side effects such as the potentially lethal cytokine release syndrome. Here the authors show that the T cell antigen coupler (TAC), a chimeric receptor that co-opts the endogenous TCR, induces more efficient anti-tumor responses and reduced toxicity when compared with past-generation CARs. TAC-engineered T cells induce robust and antigen-specific cytokine production and cytotoxicity in vitro, and strong anti-tumor activity in a variety of xenograft models including solid and liquid tumors. In a solid tumor model, TAC-T cells outperform CD28-based CAR-T cells with increased anti-tumor efficacy, reduced toxicity, and faster tumor infiltration. Intratumoral TAC-T cells are enriched for Ki-67+ CD8+ T cells, demonstrating local expansion. These results indicate that TAC-T cells may have a superior therapeutic index relative to CAR-T cells.

Pubmed ID: 30076299

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