High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells.
10.1007/s11684-018-0677-1
- Author:
Synat KANG
1
;
Yanyan LI
1
;
Yifeng BAO
1
;
Yi LI
2
Author Information
1. State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
2. State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China. li_yi@gibh.ac.cn.
- Publication Type:Journal Article
- Keywords:
TCR-CAT;
cancer immunotherapy;
cytokine-activated T cells;
high-affinity T cell receptor
- MeSH:
Cell Line, Tumor;
Cytokines;
metabolism;
Cytotoxicity, Immunologic;
Genetic Engineering;
HLA-A2 Antigen;
metabolism;
Humans;
Immunotherapy, Adoptive;
methods;
Lymphocyte Activation;
Receptors, Antigen, T-Cell;
genetics;
immunology;
T-Lymphocytes;
immunology
- From:
Frontiers of Medicine
2019;13(1):69-82
- CountryChina
- Language:English
-
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 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.
