Construction of CAR-T cells targeting CS1 and analysis of their antitumor activity in vitro.
- Author:
Weiguang ZHANG
1
;
Chunling WANG
2
;
Zhibo TAO
2
;
Changlin YIN
1
;
Jimin GAO
2
Author Information
- Publication Type:Journal Article
- Keywords: 4-1BB; CAR-T; gene therapy; human signaling lymphocyte activation family 7 (SLAMF7/CS1); inducible co-stimulator; multiple myeloma
- MeSH: 4-1BB Ligand/metabolism*; Cell Line, Tumor; Genetic Engineering; Humans; Inducible T-Cell Co-Stimulator Protein/metabolism*; Multiple Myeloma/therapy*; Signal Transduction; T-Lymphocytes/chemistry*; Xenograft Model Antitumor Assays
- From: Chinese Journal of Biotechnology 2020;36(10):2162-2170
- CountryChina
- Language:Chinese
- Abstract: We constructed the CS1-targeted second- and third-generation CAR-T cells with genetic engineered 4-1BB or/and ICOS as a costimulatory signaling molecule by use of lentiviral platform. The CS1-targeted second-generation CAR-T cells with ICOS or 4-1BB had similar anti-neoplastic activity. When effector/target ratio was 1:1, the CAR-T cells with ICOS showed better killing effect on IM9-lucgfp cells than those with 4-1BB. However, The CS1-targeted third-generation CAR-T cells exihibited lower cytolytic capacity against IM9-lucgfp cells than the CS1-targeted second-generation CAR-T cells when the ratio of effector/target was 1:1, 2:1 or 5:1. When the ratio of effector/target was 10:1, the killing efficacy of both the second- and third-generation CAR-T cells against IM9-lucgfp cells was more than 85%, significantly higher than that of the control T cells. Taken together, both the CS1-targeted second- and third-generation CAR-T cells with ICOS or/and 4-1BB could efficiently kill CS1-positive multiple myeloma cells, but the CS1-targeted second-generation CAR-T cells had more potent killing effect on CS1-positive multiple myeloma cells than the CS1-targeted third-generation CAR-T cells.
