The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity Academic Article uri icon

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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.

authors

  • Helsen, Christopher W
  • Hammill, Joanne A
  • Lau, Vivian WC
  • Mwawasi, Kenneth A
  • Afsahi, Arya
  • Bezverbnaya, Ksenia
  • Newhook, Lisa
  • Hayes, Danielle L
  • Aarts, Craig
  • Bojovic, Bojana
  • Denisova, Galina F
  • Kwiecien, Jackek Michael
  • Brain, Ian
  • Derocher, Heather
  • Milne, Katy
  • Nelson, Brad H
  • Bramson, Jonathan

publication date

  • December 2018

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