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- Title
The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity.
- Authors
Helsen, Christopher W.; Hammill, Joanne A.; Lau, Vivian W. C.; Mwawasi, Kenneth A.; Afsahi, Arya; Bezverbnaya, Ksenia; Newhook, Lisa; Hayes, Danielle L.; Aarts, Craig; Bojovic, Bojana; Denisova, Galina F.; Kwiecien, Jacek M.; Brain, Ian; Derocher, Heather; Milne, Katy; Nelson, Brad H.; Bramson, Jonathan L.
- Abstract
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. Chimeric antigen receptors (CARs) are effective tools for directing T cell killing of tumors, but may cause adverse side effects. Here the authors show that coupling of antigen-recognition and CD3-binding in a modular format induces more efficient anti-tumour responses but reduced toxicity when compared with current CARs.
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-05395-y