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

被引:81
|
作者
Li, He [1 ,2 ]
Huang, Yao [3 ]
Jiang, Du-Qing [4 ]
Cui, Lian-Zhen [4 ]
He, Zhou [4 ]
Wang, Chao [4 ]
Zhang, Zhi-Wei [4 ]
Zhu, Hai-Li [5 ]
Ding, Yong-Mei [6 ]
Li, Lin-Fang [4 ,5 ]
Li, Qiang [1 ,2 ,7 ]
Jin, Hua-Jun [4 ,5 ]
Qian, Qi-Jun [4 ,5 ,6 ]
机构
[1] Second Mil Med Univ, Changhai Hosp, Dept Resp Med, Shanghai 200438, Peoples R China
[2] Second Mil Med Univ, Changhai Hosp, Dept Crit Care Med, Shanghai 200438, Peoples R China
[3] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Biliary Tract Surg, Shanghai 200438, Peoples R China
[4] Shanghai Cell Therapy Res Inst, Shanghai 201805, Peoples R China
[5] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Lab Gene & Viral Therapy, Shanghai 200438, Peoples R China
[6] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Biotherapy, Shanghai 200438, Peoples R China
[7] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Dept Resp & Crit Care Med, Shanghai 200080, Peoples R China
来源
CELL DEATH & DISEASE | 2018年 / 9卷
基金
中国国家自然科学基金;
关键词
ANTILEUKEMIC POTENCY; IMMUNOTHERAPY; REMISSIONS; AFFINITY; TARGET;
D O I
10.1038/s41419-017-0238-6
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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-CD3 zeta 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.
引用
收藏
页数:11
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