Details

Autor(en) / Beteiligte

• Lv, Jiang
• Zhao, Ruocong
• Wu, Di
• Zheng, Diwei
• Wu, Zhiping
• Shi, Jingxuan
• Wei, Xinru
• Wu, Qiting
• Long, Youguo
• Lin, Simiao
• Wang, Suna
• Wang, Zhi
• Li, Yang
• Chen, Yantao
• He, Qing
• Chen, Suimin
• Yao, Huihui
• Liu, Zixia
• Tang, Zhaoyang
• Yao, Yao
• Pei, Duanqing
• Liu, Pentao
• Zhang, Xuchao
• Zhang, Zhenfeng
• Cui, Shuzhong
• Chen, Ren
• Li, Peng

Titel

Mesothelin is a target of chimeric antigen receptor T cells for treating gastric cancer

Ist Teil von

• Journal of hematology and oncology, 2019-02, Vol.12 (1), p.18-18, Article 18

Ort / Verlag

England: BioMed Central Ltd

Erscheinungsjahr

2019

Link zum Volltext

Quelle

SpringerLink (Online service)

Beschreibungen/Notizen

• Gastric cancer (GC) is a common cancer in Asia and currently lacks a targeted therapy approach. Mesothelin (MSLN) has been reported to be expressed in GC tissue and could be targeted by chimeric antigen receptor (CAR) T cells. Mesothelin targeting CAR-T has been reported in mesothelioma, lung cancer, breast cancer, and pancreas cancer. However, the feasibility of using anti-MSLN CAR T cells to treat GC remains to be studied. We verified MSLN expression in primary human GC tissues and GC cell lines and then redirected T cells with a CAR containing the MSLN scFv (single-chain variable fragment), CD3ζ, CD28, and DAP10 intracellular signaling domain (M28z10) to target MSLN. We evaluated the function of these CAR T cells in vitro in terms of cytotoxicity, cytokine secretion, and surface phenotype changes when they encountered MSLN+ GC cells. We also established four different xenograft GC mouse models to assess in vivo antitumor activity. M28z10 T cells exhibited strong cytotoxicity and cytokine-secreting ability against GC cells in vitro. In addition, cell surface phenotyping suggested significant activation of M28z10 T cells upon target cell stimulation. M28z10 T cells induced GC regression in different xenograft mouse models and prolonged the survival of these mice compared with GFP-transduced T cells in the intraperitoneal and pulmonary metastatic GC models. Importantly, peritumoral delivery strategy can lead to improved CAR-T cells infiltration into tumor tissue and significantly suppress the growth of GC in a subcutaneous GC model. These results demonstrate that M28z10 T cells possess strong antitumor activity and represent a promising therapeutic approach to GC.