决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:A CD123-specific chimeric antigen receptor augments anti-acute myeloid leukemia activity of Vγ9Vδ2 T cells.
A CD123-specific chimeric antigen receptor augments anti-acute myeloid leukemia activity of Vγ9Vδ2 T cells.
目的:探讨表达抗CD123嵌合抗原受体(CAR)的Vγ9Vδ2 T细胞是否可作为急性髓系白血病(AML)治疗的替代方案。
目的:探讨表达抗CD123嵌合抗原受体(CAR)的Vγ9Vδ2 T细胞是否可作为急性髓系白血病(AML)治疗的替代方案。材料与方法:将体外扩增的Vγ9Vδ2 T细胞电穿孔导入编码抗CD123 CAR的mRNA。通过体外细胞毒性、脱颗粒及细胞因子释放水平检测修饰后Vγ9Vδ2 T细胞的效应功能和特异性。采用NOD-SCID-γc-/-小鼠的KG1-luc异种移植模型分析体内功能。结果:修饰后的Vγ9Vδ2 T细胞在体外对AML细胞系和原代AML细胞均表现出显著增强的效应活性。在异种移植小鼠模型中,修饰后的Vγ9Vδ2细胞显示出增强的肿瘤控制能力。结论:表达抗CD123 CAR的Vγ9Vδ2 T细胞可能成为靶向AML的替代方法。
Aim: To investigate whether anti-CD123 chimeric antigen receptor (CAR)-expressing Vγ9Vδ2 T cells could be an alternative for acute myeloid leukemia (AML) treatment. Materials & methods: Ex vivo expanded Vγ9Vδ2 T cells were electroporated with anti-CD123 CAR-encoding mRNA. The effector function and specificity of the modified Vγ9Vδ2 T cells were examined by in vitro cytotoxicity, degranulation and cytokine release level. The in vivo function was analyzed using the xenograft KG1-luc model with NOD-SCID-γc-/- mice. Results: The modified Vγ9Vδ2 T cells exhibited significantly improved effector activities against both AML cell lines and primary AML cells in vitro . In the xenograft mouse model, the modified Vγ9Vδ2 cells displayed an enhanced tumor control potency. Conclusion: Anti-CD123 CAR-expressing Vγ9Vδ2 T cells may serve as an alternative way to target AML.
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