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
  • 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. [email protected].
  • 7. Department of Respiratory and Critical Care Medicine, Shanghai First People's Hospital, Shanghai Jiaotong University, 200080, Shanghai, China. [email protected].
  • 8. Shanghai Cell Therapy Research Institute, 201805, Shanghai, China. [email protected].
  • 9. Laboratory of Gene and Viral Therapy, The Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 200438, Shanghai, China. [email protected].
  • 10. Shanghai Cell Therapy Research Institute, 201805, Shanghai, China. [email protected].
  • 11. Laboratory of Gene and Viral Therapy, The Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 200438, Shanghai, China. [email protected].
  • 12. Department of Biotherapy, The Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 200438, Shanghai, China. [email protected].
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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