In Vitro Generation of Stem Cell Memory-Like T Cells from Activated T Cells
In Vitro Generation of Stem Cell Memory-Like T Cells from Activated T Cells
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DOI：
10.1007/978-1-0716-0266-9_11
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发表时间：
2020-01-01
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影响因子：
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通讯作者：
Kondo, Taisuke
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文献类型：
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作者：
Ando, Makoto;Ikeda, Mari;Kondo, Taisuke
免疫T细胞疗法是一种有吸引力的癌症免疫治疗策略。体外扩增的肿瘤相关抗原（TAA）特异性T细胞可以有效地对抗原始肿瘤细胞。嵌合抗原受体工程化T（CAR-T）细胞也被证明是血液恶性肿瘤的有希望的疗法。然而，这些基于T细胞的疗法的限制之一是在体外活化期间和/或在体内转移后快速获得T细胞的耐受（无反应性、缺失、功能障碍和/或耗尽）表型。我们和其他人发现，干细胞记忆T（T-SCM）细胞对这种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。在这里，我们描述了一种用于产生表型T-SCM样细胞（iT（SCM）细胞）的方案，其可以通过活化T细胞与表达Notch配体的OP 9基质细胞的简单共培养来诱导。我们还展示了利用NSG小鼠进行肿瘤免疫治疗的方法。
Adoptive T-cell therapy is an attractive strategy for cancer immunotherapy. The transfer of in vitro expanded tumor-associated antigen (TAA)-specific T cells from patients may effectively fight against the original tumor cells. The chimeric antigen receptor-engineered T (CAR-T) cells are also shown to be a promising therapy for hematologic malignancies. However, one of the limitations of these T-cell-based therapies is a rapid acquisition of tolerant (anergy, deletion, dysfunctional and/or exhausted) phenotypes of T cells during activation in vitro and/or after transfer in vivo. We and others found that stem cell memory T (T-SCM) cells are strongly resistant against such tolerance, showing strong expansion and persistence in vivo, and provide long-lasting antitumor effects. Here we describe a protocol for the generation of phenotypically T-SCM-like cells (iT(SCM) cells), which can be induced by simple co-culture of activated T cells with OP9 stroma cells expressing a Notch ligand. We also showed the methods of cancer immunotherapy by using NSG mice.