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

• Published in: Cell death & disease Vol. 9; no. 2; pp. 177 - 11
• Main Authors: Li, He, Huang, Yao, Jiang, Du-Qing, Cui, Lian-Zhen, He, Zhou, Wang, Chao, Zhang, Zhi-Wei, Zhu, Hai-Li, Ding, Yong-Mei, Li, Lin-Fang, Li, Qiang, Jin, Hua-Jun, Qian, Qi-Jun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.02.2018; Springer Nature B.V
• Subjects: 13; 38; 38/22; 38/23; 38/77; 45; 45/90; 45/91; 96/31; Adoptive immunotherapy; Antibodies; Antigens; Antitumor activity; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Chimeric antigen receptors; Epidermal growth factor; Epidermal growth factor receptors; Immunology; Immunotherapy; Intracellular signalling; Life Sciences; Lung cancer; Lungs; Lymphocytes; Lymphocytes T; Non-small cell lung carcinoma; Xenografts
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-017-0238-6

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.