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High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells

  • Synat Kang
  • Yanyan Li
  • Yifeng Bao
  • Yi LiEmail author
Open Access
Research Article
  • 60 Downloads

Abstract

Cytokine-activated T cells (CATs) can be easily expanded and are widely applied to cancer immunotherapy. However, the good efficacy of CATs is rarely reported in clinical applications because CATs have no or very low antigen specificity. The low-efficacy problem can be resolved using T cell antigen receptor-engineered CAT (TCR-CAT). Herein, we demonstrate that NY-ESO-1157–165 HLA-A*02:01-specific high-affinity TCR (HAT)-transduced CATs can specifically kill cancer cells with good efficacy. With low micromolar range dissociation equilibrium constants, HAT-transduced CATs showed good specificity with no off-target killing. Furthermore, the high-affinity TCR-CATs delivered significantly better activation and cytotoxicity than the equivalent TCR-engineered T cells (TCR-Ts) in terms of interferon-γ and granzyme B production and in vitro cancer cell killing ability. TCR-CAT may be a very good alternative to the expensive TCR-T, which is considered an effective personalized cyto-immunotherapy.

Keywords

cytokine-activated T cells high-affinity T cell receptor cancer immunotherapy TCR-CAT 

Notes

Acknowledgements

This study was supported by the Sciences and Technology Program of Guangzhou (No. 201504010016); the National Key R&D program (No. 2016YFC1303404); and the Sciences and Technology Program of Guangzhou (No. 201704020220). The study was also sponsored by the CAS-TWAS President’s PhD Fellowship Program awarded to Synat Kang.

Supplementary material

11684_2018_677_MOESM1_ESM.pdf (750 kb)
Supplementary material, approximately 751 KB.

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Copyright information

© The Author(s) 2019

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the appropriate credit is given to the original author(s) and the source, and a link is provided to the Creative Commons license, indicating if changes were made.

Authors and Affiliations

  1. 1.State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina
  2. 2.University of Chinese Academy of SciencesBeijingChina

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