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Dual-function chimeric antigen receptor T cells targeting c-Met and PD-1 exhibit potent anti-tumor efficacy in solid tumors

Invest New Drugs. 2020; 
Xingxing Yuan, Zujun Sun, Qingyun Yuan, Weihua Hou, Qiaoyan Liang, Yuxiong Wang, Wei Mo, Huijie Wang, Min Yu
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Recombinant Antibody Expression … Primary human T cells were cultured in RPMI 1640-media (Sigma, Shanghai, China) containing recombinant human IL-2 (30 IU/ml; GenScript, cat# Z00368–1). MKN45, HGC27, PC9, and 293 T were maintained in Dulbecco's modified Eagle's medium (Gibco, China) … Get A Quote

摘要

Purpose Programmed cell death 1 (PD-1), which is upregulated under the continuous induction of the tumor microenvironment, causes chimeric antigen receptor (CAR)-T cell hypofunction via interaction with programmed death ligand 1 (PD-L1). This study aimed to construct CAR-T cells that are resistant to PD-1 inhibition to improve the effect of CAR-T cells in solid tumors. Methods We constructed a type of dual-function CAR-T cell that targets tumor-associated antigen c-Met and blocks the binding of PD-1 with PD-L1. The expression of c-Met, PD-L1, and inhibitory receptors was measured using flow cytometry. The cytotoxicity, cytokine release, and differentiation level of CAR-T cells were determined using lactate dehy... More

关键词

C-Met, Cancer immunotherapy, Chimeric antigen receptor, PD-1, Tumor microenvironment