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 and Jonathan L. Bramson ()
Additional contact information
Christopher W. Helsen: McMaster University
Joanne A. Hammill: McMaster University
Vivian W. C. Lau: McMaster University
Kenneth A. Mwawasi: McMaster University
Arya Afsahi: McMaster University
Ksenia Bezverbnaya: McMaster University
Lisa Newhook: McMaster University
Danielle L. Hayes: McMaster University
Craig Aarts: McMaster University
Bojana Bojovic: McMaster University
Galina F. Denisova: McMaster University
Jacek M. Kwiecien: McMaster University
Ian Brain: McMaster University
Heather Derocher: British Columbia Cancer Agency
Katy Milne: British Columbia Cancer Agency
Brad H. Nelson: British Columbia Cancer Agency
Jonathan L. Bramson: McMaster University

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05395-y

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