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工程化 mRNA CAR-T 细胞用于癌症免疫治疗

英文原题:Engineering mRNA CAR-T Cells for Cancer Immunotherapy.

查看英文原题

Engineering mRNA CAR-T Cells for Cancer Immunotherapy.

PubMed 2025/01/01(内容时间) Methods Mol Biol

研究概要

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。

中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
Almåsbak H、Sioud M、Rasmussen AM
第一作者单位
Cellular Medicine, Bioproduction, Thermo Fisher Scientific, Oslo, Norway.Norway
通讯作者单位
Division of Cancer Medicine, Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway. mosioud@medisin.uio.no.Norway
期刊
Methods in molecular biology (Clifton, N.J.)2025
原文标识
PubMed 40877511 · DOI 10.1007/978-1-0716-4742-4_14