Double-targeting chimeric antigen receptor, encoding gene and recombinant expression vector

The invention discloses a double-targeting chimeric antigen receptor, which comprises a double-antigen binding region, a first hinge region, a chimeric antigen receptor T cell activation domain and a protein co-expression self-cleavage domain which are sequentially connected in series, and the doubl...

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Bibliographische Detailangaben
Hauptverfasser: JIANG LIYING, WAN GUOQING, GU XUEFENG, SHI PING, CHEN CHUNZHOU, CHEN NIANHONG
Format: Patent
Sprache:chi ; eng
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Zusammenfassung:The invention discloses a double-targeting chimeric antigen receptor, which comprises a double-antigen binding region, a first hinge region, a chimeric antigen receptor T cell activation domain and a protein co-expression self-cleavage domain which are sequentially connected in series, and the double-antigen binding region comprises a heavy chain VH and a light chain VL of an MSLN and MUC1 single-chain antibody which are connected in series, and a second hinge region connected with the MSLN and the MUC1 single-chain antibody. The double-targeting CAR-T cell can kill tumor cells expressing double antigens, killing is more accurate and efficient, meanwhile, the off-target effect is reduced or avoided, the side effect of non-specific killing is reduced, and the anti-tumor effect is enhanced. 本发明公开了一种双靶向嵌合抗原受体,包括依次串联连接的双抗原结合区、第一铰链区、嵌合抗原受体T细胞激活域和蛋白共表达自剪切域,所述双抗原结合区包括以串联方式连接的MSLN、MUC1单链抗体的重链VH和轻链VL、及连接MSLN、MUC1单链抗体的第二铰链区。本发明的双靶向CAR-T细胞能杀伤表达双抗原的肿瘤细胞,使杀伤更为精准高效,同时降低或避免了"脱靶效应"的发生,降低了非特异杀伤的副作用,增强了抗肿瘤功效。