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用于治疗多发性骨髓瘤的第二代 CD38-CAR-T 细胞

英文原题:A second-generation CD38-CAR-T cell for the treatment of multiple myeloma.

查看英文原题

A second-generation CD38-CAR-T cell for the treatment of multiple myeloma.

PubMed 2023/04/11(内容时间) Cancer Med Q2 · IF 3.5(JCR 2025)

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研究概要

这些结果提示 CD38-CAR-T 细胞是治疗 MM 的一种有前景的治疗策略。

中文摘要

多发性骨髓瘤(MM)是侵袭性浆细胞恶性肿瘤,每年造成全球大量死亡;CAR转导T细胞疗法是治疗血液肿瘤的有前景免疫疗法。

研究者构建第二代靶向CD38 CAR并制备CAR-T,评估其对MM细胞系的作用。

体外实验中,CD38 CAR-T 对MM细胞系和原代MM细胞的细胞毒作用均强于对照T细胞。即使效靶比为1:100,仍可杀死超过50%的MM1.s和RPMI8226细胞;对原代MM细胞也有增强杀伤。CAR-T 可依赖靶抗原活化并产生多种细胞因子。体内实验显示,CAR-T 在异种移植小鼠模型中具有显著抗肿瘤效果。

结果支持CD38 CAR-T 作为治疗MM的有前景策略。

展开英文摘要原文

Multiple myeloma (MM) is an aggressive plasma cell malignancy, causing a number of deaths worldwide every year. Chimeric antigen receptor (CAR) transduced T-cell therapy has been a promising immunotherapy against hematological malignancies.

In this study, we developed a second-generation CAR construct and generated CAR-T cells targeting CD38 molecule. Then effects of CAR-T cells against MM cell lines were evaluated.

CD38-CAR-T cells showed higher cytotoxicity to MM cell lines and primary MM cells than that of control T cells in vitro. Over 50% MM1.s and RPMI8226 cells were killed by CAR-T cells even at effector to target ratio of 1:100. CAR-T cells also showed an enhanced cytotoxicity against primary MM cells. CAR-T cells could be activated and produced a variety of cytokines in a target-dependent manner. In vivo test indicated that CAR-T cells also showed significant antitumor effect on xenograft mice models.

These results indicated a promising therapeutic strategy of CD38-CAR-T cells against MM.

论文信息

作者
Li H、Li J、Wu J、Shi Z、Gao Y、Song W、Li J、Li Z
单位
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.China
文献类型
非美国政府资助研究
期刊
Cancer medicine2023 May
原文标识
PubMed 37039305 · DOI 10.1002/cam4.5818