Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice

EGFR特异性CAR T细胞在体外和小鼠体内对非小细胞肺癌细胞的抗肿瘤活性

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作者:He Li ,Yao Huang ,Du-Qing Jiang ,Lian-Zhen Cui ,Zhou He ,Chao Wang ,Zhi-Wei Zhang ,Hai-Li Zhu ,Yong-Mei Ding ,Lin-Fang Li ,Qiang Li ,Hua-Jun Jin ,Qi-Jun Qian

Abstract

Effective control of non-small-cell lung cancer (NSCLC) remains clinically challenging, especially during advanced stages of the disease. This study developed an adoptive T-cell treatment through expression of a chimeric antigen receptor (CAR) to target human epidermal growth factor receptor (EGFR) in NSCLC. We optimized the non-viral piggyBac transposon system to engineer human T cells for the expression of EGFR-CAR, consisting of EGFR scFv, transmembrane domain, and intracellular 4-1BB-CD3ζ signaling domains. The modified CAR T cells exhibited expansion capability and anticancer efficacy in a time- and antigen-dependent manner in vitro as well as regression of EGFR-positive human lung cancer xenografts in vivo. EGFR-CAR T therapy is a promising strategy to improve the efficacy and potency of the adoptive immunotherapy in NSCLC. Moreover, EGFR-CAR T therapy could become a clinical application for NSCLC patients in the future.

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