chimeric antigen receptor-modified t cells redirected to epha2 for the immunotherapy of non-small cell lung cancer
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ID: 218179
2018
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Abstract
Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) is overexpressed in more than 90% of non-small cell lung cancer (NSCLC) but not significantly in normal lung tissue. It is therefore an important tumor antigen target for chimeric antigen receptors (CAR)-T-based therapy in NSCLC. Here, we developed a specific CAR targeted to EphA2, and the anti-tumor effects of this CAR were investigated. A second generation CAR with co-stimulatory receptor 4-1BB targeted to EphA2 was developed. The functionality of EphA2-specific T cells in vitro was tested with flow cytometry and real-time cell electronic sensing system assays. The effect in vivo was evaluated in xenograft SCID Beige mouse model of EphA2 positive NSCLC. These EphA2-specifc T cells can cause tumor cell lysis by producing the cytokines IFN-γ when cocultured with EphA2-positive targets, and the cytotoxicity effects was specific in vitro. In vivo, the tumor signals of mice treated with EphA2-specifc T cells presented the tendency of decrease, and was much lower than the mice treated with non-transduced T cells. The anti-tumor effects of this CAR-T technology in vivo and vitro had been confirmed. Thus, EphA2-specific T-cell immunotherapy may be a promising approach for the treatment of EphA2-positive NSCLC.
| Reference Key |
li2018translationalchimeric
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| Authors | ;Ning Li;Shaohui Liu;Mingjiao Sun;Wei Chen;Xiaogang Xu;Zhu Zeng;Yemin Tang;Yongquan Dong;Alex H. Chang;Qiong Zhao |
| Journal | advances in acoustics and vibration |
| Year | 2018 |
| DOI |
10.1016/j.tranon.2017.10.009
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