1. Academic Validation
  2. Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice

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

  • Cell Death Dis. 2018 Feb 7;9(2):177. doi: 10.1038/s41419-017-0238-6.
He Li 1 Yao Huang 2 Du-Qing Jiang 3 Lian-Zhen Cui 3 Zhou He 3 Chao Wang 3 Zhi-Wei Zhang 3 Hai-Li Zhu 4 Yong-Mei Ding 5 Lin-Fang Li 3 4 Qiang Li 6 7 Hua-Jun Jin 8 9 Qi-Jun Qian 10 11 12
Affiliations

Affiliations

  • 1 Departments of Respiratory and Critical Care Medicine, Changhai Hospital, The Second Military Medical University, 200438, Shanghai, China.
  • 2 Department of Biliary Tract Surgery I, The Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 200438, Shanghai, China.
  • 3 Shanghai Cell Therapy Research Institute, 201805, Shanghai, China.
  • 4 Laboratory of Gene and Viral Therapy, The Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 200438, Shanghai, China.
  • 5 Department of Biotherapy, The Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 200438, Shanghai, China.
  • 6 Departments of Respiratory and Critical Care Medicine, Changhai Hospital, The Second Military Medical University, 200438, Shanghai, China. qiangli19621217@126.com.
  • 7 Department of Respiratory and Critical Care Medicine, Shanghai First People's Hospital, Shanghai Jiaotong University, 200080, Shanghai, China. qiangli19621217@126.com.
  • 8 Shanghai Cell Therapy Research Institute, 201805, Shanghai, China. hj-jin@hotmail.com.
  • 9 Laboratory of Gene and Viral Therapy, The Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 200438, Shanghai, China. hj-jin@hotmail.com.
  • 10 Shanghai Cell Therapy Research Institute, 201805, Shanghai, China. qianqj@sino-gene.cn.
  • 11 Laboratory of Gene and Viral Therapy, The Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 200438, Shanghai, China. qianqj@sino-gene.cn.
  • 12 Department of Biotherapy, The Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 200438, Shanghai, China. qianqj@sino-gene.cn.
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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