In Vitro Conversion of Activated T Cells into Stem Cell Memory-Like T Cells.

In Vitro Conversion of Activated T Cells into Stem Cell Memory-Like T Cells.
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激活的 T 细胞在体外转化为干细胞记忆样 T 细胞。

DOI:
10.1007/978-1-4939-9728-2_4
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发表时间:
2019
期刊:
Methods Mol Biol
影响因子:
--
通讯作者:
Yoshimura A
Yoshimura A
中科院分区:
--
文献类型:
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作者:
Kondo T;Imura Y;Ando M;Chikuma S;Yoshimura A

文献摘要

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免疫性T细胞治疗是肿瘤免疫治疗中一个有吸引力的策略。体外扩增的肿瘤相关抗原(TAA)特异性T细胞的转移可以有效地破坏原始肿瘤细胞。限制之一是快速获得耐受(无反应性、缺失、功能障碍和/或衰竭)表型。我们和其他人发现,干细胞记忆T(TSCM)细胞对耐受性有很强的抵抗力,在体内表现出很强的扩增和持久性,并提供持久的抗肿瘤作用。我们先前建立了表型TSCM细胞(iTSCM)可以使用活化的T细胞与表达Notch配体的0 P9基质细胞的简单共培养物来诱导。在这里,我们描述了一个定义的协议,用于产生人类iTSCM细胞,包括试剂,培养设置,和程序。
Adoptive T cell therapy is an attractive strategy in tumor immunotherapy. The transfer of in vitro expanded tumor-associated antigen (TAA)-specific T cells from patients may effectively destroy the original tumor cells. One of the limitations is a rapid acquisition of tolerant (anergy, deletion, dysfunctional, and/or exhausted) phenotypes. We and others found that stem cell memory T (TSCM) cells are strongly resistant to tolerance, showing strong expansion and persistence in vivo and providing long-lasting antitumor effects. We previously established that phenotypically TSCMcells (iTSCM) can be induced using a simple coculture of activated T cells with OP9 stroma cells expressing a Notch ligand. Here, we describe a defined protocol for generating human iTSCMcells, including reagents, culture setting, and procedure.