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.
- 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].
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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