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:Engineering mRNA CAR-T Cells for Cancer Immunotherapy.
Engineering mRNA CAR-T Cells for Cancer Immunotherapy.
过继 T 细胞治疗是一种有前景的癌症免疫疗法,但分离肿瘤特异性细胞毒性 T 细胞耗时且常常失败。
过继T细胞疗法是有前景的癌症免疫治疗方法,但分离肿瘤特异性细胞毒性T细胞耗时较长,而且常常无法成功。另一种方法是通过基因改造,使T细胞表达肿瘤抗原特异性T细胞受体(TCR)或嵌合抗原受体(CAR),从而引导大量免疫细胞靶向恶性细胞。CAR结合了抗体来源的单链可变片段的特异性和T细胞信号结构域(如CD3ζ、CD28、4-1BB),使T细胞能够以不依赖MHC的方式识别并杀伤抗原阳性癌细胞。本章介绍大规模扩增T细胞,以及利用电穿孔递送方法中规模制备信使RNA(mRNA)CAR-T细胞的实验流程。采用两种CAR作为模型系统:一种靶向CD19,另一种靶向血液系统恶性肿瘤和实体瘤中表达的抗原。
Adoptive T-cell therapy is a promising cancer immunotherapy, but isolating tumor-specific cytotoxic T cells is time-consuming and often unsuccessful. An alternative approach involves genetically modifying T cells to express tumor antigen-specific T-cell receptors (TCRs) or chimeric antigen receptors (CARs), enabling the redirection of large numbers of immune cells to target malignant cells. CARs combine the specificity of antibody-derived single-chain variable fragments with T-cell signaling domains (e.g., CD3 , CD28, 4-1BB), enabling T cells to recognize and kill antigen-positive cancer cells in an MHC-independent manner. This chapter outlines protocols for large-scale T-cell expansion and medium-scale production of messenger RNA (mRNA) CAR-T cells using electroporation as a delivery method. Two CARs are used as model systems: one targeting CD19 and another targeting an antigen expressed on hematological malignancies and solid tumors.
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