Construction of CD38/CD138 dual-targeted CAR-T cell and it's in vitro cytotoxicity against multiple myeloma cells
10.3872/j.issn.1007-385x.2024.12.003
- VernacularTitle:双靶点CD38/CD138 CAR-T细胞的构建及其对多发性骨髓瘤细胞的体外杀伤效果
- Author:
Lu PAN
1
;
Hangyu LIU
;
Jinghong WANG
;
Dawei SUN
;
Songbo ZHAO
;
Jiyu JU
;
Xuanli SONG
Author Information
1. 山东第二医科大学基础医学院 免疫学教研室,山东 潍坊 261053;山东第一医科大学附属省立医院 临床医学检验部,山东 济南 250021
- Publication Type:Journal Article
- Keywords:
multiple myeloma(MM);
chimeric antigen receptor gene-modified T lymphocyte(CAR-T cell);
CD38/CD138 CAR-T cell;
immunotherapy
- From:
Chinese Journal of Cancer Biotherapy
2024;31(12):1186-1193
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To construct dual-targeting(CD38 and CD138)chimeric antigen receptor(CAR)gene-modified T cells(CD38/CD138 CAR-T cells)and explore their in vitro cytotoxicity against multiple myeloma(MM)cells.Methods:Based on the high expression of CD38 and CD138 antigens in MM cells,CD38 CAR-T cells and CD138 CAR-T cells targeting CD38 and CD138 respectively,and CD38/CD138 dual-targeted CAR-T cells targeting both CD38 and CD138 were constructed using CAR-T cell technology.The experimental groups included untreated T cells,CD38 CAR-T,CD138 CAR-T,and CD38/CD138 CAR-T cells.The phenotype of CAR-T cells was detected by flow cytometry.The cytotoxicity of various CAR-T cells against MM cells(RPMI8226 and U266)was assessed using the LDH release assay.Results:Three types of CAR-T cells,CD38 CAR-T,CD138 CAR-T,and CD38/CD138 CAR-T cells,were successfully constructed.The CD38/CD138 CAR-T cells tended to differentiate into a memory phenotype,expressing higher levels of proliferation marker(CD25),activation marker(CD27),and lower levels of exhaustion markers(PD-1,CTLA-4,TIM-3)(all P<0.001).Moreover,CD38/CD138 CAR-T cells were less prone to exhaustion and senescence,and expressed lower levels of r-H2AX,p-p53,p21,and p16 proteins(all P<0.01).Under different effector-to-target cell ratios,CD38/CD138 CAR-T cells exhibited stronger cytotoxic effects against RPMI8226 and U266 cells compared to CD38 CAR-T and CD138 CAR-T cells(all P<0.001).Conclusion:CD38/CD138 CAR-T cells targeting both CD38 and CD138 demonstrate an optimal phenotype and enhanced anti-tumor activity in vitro,offering promising potential for immunotherapy in multiple myeloma.
