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

doi:10.1007/s11684-018-0677-1

Frontiers of Medicine

2019, Vol. 13

Issue (1): 69-82 https://doi.org/10.1007/s11684-018-0677-1

本期目录

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

Synat Kang^1,², Yanyan Li¹, Yifeng Bao¹, Yi Li^1,²(

)

¹. State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
². University of Chinese Academy of Sciences, Beijing 100049, China

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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-1_157–165 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-g 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.

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

收稿日期: 2018-05-04 出版日期: 2019-03-12

Corresponding Author(s): Yi Li

引用本文:

. [J]. Frontiers of Medicine, 2019, 13(1): 69-82.
Synat Kang, Yanyan Li, Yifeng Bao, Yi Li. High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells. Front. Med., 2019, 13(1): 69-82.

链接本文:

https://academic.hep.com.cn/fmd/CN/10.1007/s11684-018-0677-1
https://academic.hep.com.cn/fmd/CN/Y2019/V13/I1/69

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