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用编码CXCR2的mRNA转染肿瘤浸润性T细胞。

Transfection of Tumor-Infiltrating T Cells with mRNA Encoding CXCR2.

作者信息

Idorn Manja, Thor Straten Per, Svane Inge Marie, Met Özcan

机构信息

Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, 2730, Herlev, Denmark.

Department of Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, 2730, Herlev, Denmark.

出版信息

Methods Mol Biol. 2016;1428:261-76. doi: 10.1007/978-1-4939-3625-0_17.

Abstract

Adoptive T-cell therapy based on the infusion of patient's own immune cells after ex vivo culturing is among the most potent forms of personalized treatment among recent clinical developments for the treatment of cancer. However, despite high rates of successful initial clinical responses, only about 20 % of patients with metastatic melanoma treated with tumor-infiltrating lymphocytes (TILs) enter complete and long-term regression, with the majority either relapsing after initial partial regression or not benefiting at all. Previous studies have shown a positive correlation between the number infused T cells migrating to the tumor and the clinical response, but also that only a small fraction of adoptively transferred T cells reach the tumor site. In this chapter, we describe a protocol for transfection of TILs with mRNA encoding the chemokine receptor CXCR2 transiently redirecting and improving TILs migration toward tumor-secreted chemokines in vitro.

摘要

基于体外培养后输注患者自身免疫细胞的过继性T细胞疗法,是近期癌症治疗临床进展中最有效的个性化治疗形式之一。然而,尽管初始临床反应成功率很高,但接受肿瘤浸润淋巴细胞(TILs)治疗的转移性黑色素瘤患者中,只有约20%实现完全和长期缓解,大多数患者要么在初始部分缓解后复发,要么根本没有获益。先前的研究表明,迁移至肿瘤的输注T细胞数量与临床反应之间存在正相关,但也表明过继转移的T细胞中只有一小部分到达肿瘤部位。在本章中,我们描述了一种用编码趋化因子受体CXCR2的mRNA转染TILs的方案,该方案可在体外短暂重定向并改善TILs向肿瘤分泌趋化因子的迁移。

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