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.
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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.
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Kang, S., Li, Y., Bao, Y. et al. High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells. Front. Med. 13, 69–82 (2019). https://doi.org/10.1007/s11684-018-0677-1
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DOI: https://doi.org/10.1007/s11684-018-0677-1