首页|期刊导航|中国肿瘤生物治疗杂志|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

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

潘璐刘航宇王景鸿孙大玮赵松柏鞠吉雨宋绚丽

中国肿瘤生物治疗杂志2024，Vol.31Issue(12)：1186-1193,8.

中国肿瘤生物治疗杂志2024，Vol.31Issue(12)：1186-1193,8.DOI:10.3872/j.issn.1007-385x.2024.12.003

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

Construction of CD38/CD138 dual-targeted CAR-T cell and it's in vitro cytotoxicity against multiple myeloma cells

潘璐 ¹刘航宇 ²王景鸿 ³孙大玮 ⁴赵松柏 ⁵鞠吉雨 ⁶宋绚丽⁷

作者信息

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
2. 临沂市莒南县人民医院检验科,山东临沂 276600
3. 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
4. 山东第一医科大学附属省立医院医学影像科,山东济南 250021
5. 山东第一医科大学附属省立医院中心实验室,山东济南 250021
6. 山东第二医科大学基础医学院免疫学教研室,山东潍坊 261053
7. 济南市疾病预防控制中心细菌性疾病检验所,山东济南 250021
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摘要

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.

关键词

多发性骨髓瘤/嵌合抗原受体基因修饰T淋巴细胞/CD38/CD138 CAR-T细胞/免疫治疗

Key words

multiple myeloma(MM)/chimeric antigen receptor gene-modified T lymphocyte(CAR-T cell)/CD38/CD138 CAR-T cell/immunotherapy

分类

医药卫生

引用本文复制引用

潘璐,刘航宇,王景鸿,孙大玮,赵松柏,鞠吉雨,宋绚丽..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[J].中国肿瘤生物治疗杂志,2024,31(12):1186-1193,8.

基金项目

山东省自然科学基金(No.ZR2023QC179) （No.ZR2023QC179）

中国肿瘤生物治疗杂志

OA北大核心CSTPCD

ISSN：1007-385X

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