文献类型：期刊文献

英文题名：The antitumor capacity of mesothelin-CAR-T cells in targeting solid tumors in mice

作者：Zhang, Qian[1];Liu, Guoping[2];Liu, Jibin[3];Yang, Mu[4];Fu, Juan[5];Liu, Guodi[1];Li, Dehua[1];Gu, Zhangjie[1];Zhang, Linsong[1];Pan, Yingjiao[1];Cui, Xingbing[1];Wang, Lu[1];Zhang, Lixin[6];Tian, Xiaoli[1]

机构：[1]Shanghai Yihao Biol Technol Co Ltd, Shanghai 200231, Peoples R China;[2]Changhai Hosp, Dept Gen Surg, Shanghai 200433, Peoples R China;[3]Nantong Tumor Hosp, Inst Tumor, 30 North Tongyang Rd, Nantong City 226361, Jiangsu, Peoples R China;[4]Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Pathol, Sch Med, Shanghai 200080, Peoples R China;[5]Dalian Med Univ, Dept Obstet & Gynecol, Affiliated Hosp 1, Dalian 116000, Peoples R China;[6]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Room 18-201,130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2021

卷号：20

起止页码：556

外文期刊名：MOLECULAR THERAPY ONCOLYTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000635158900047)】；

基金：This research was supported by Shanghai Science and Technology Committee (STCSM; grant numbers 19ZR1454700 and 202H1020600).

语种：英文

摘要：Since the approval of chimeric antigen receptor (CAR) T cell therapy targeting CD19 by the FDA, CAR-T cell therapy has received increasing attention as a new method for targeting tumors. Although CAR-T cell therapy has a good effect against hematological malignancies, it has been less effective against solid tumors. In the present study, we selected mesothelin (MSLN/MESO) as a target for CAR-T cells because it is highly expressed by solid tumors but only expressed at low levels by normal tissues. We engineered a third generation MSLN-CAR comprising a single-chain variable fragment (scFv) targeting MSLN (MSLN-scFv), a CD8 transmembrane domain, the costimulatory domains from CD28 and 4-1BB, and the activating domain CD3 zeta. In vitro, MSLN-CAR-T cells killed various solid tumor cell lines, demonstrating that it could specifically kill MSLN-positive cells and release cytokines. In vivo, we investigated the effects of MSLN-CAR-T cell therapy against ovarian, breast, and colorectal cancer cell-line-derived xenografts (CDX) and MSLN-positive colorectal and gastric cancer patient-derived xenografts (PDX). MSLN-CAR decreased the growth of MSLN-positive tumors concomitant with significantly increased T cells and cytokine levels compared to the control group. These results indicated that modified MSLN-CAR-T cells could be a promising therapeutic approach for solid tumors.