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设计用于定制癌症免疫疗法的 T 细胞和 T 细胞受体。

Designer T-cells and T-cell receptors for customized cancer immunotherapies.

机构信息

Division of Infection and Immunity, Cardiff University School of Medicine, Henry Wellcome Building, University Hospital Wales, Cardiff CF14 4XN, Wales, UK.

Division of Infection and Immunity, Cardiff University School of Medicine, Henry Wellcome Building, University Hospital Wales, Cardiff CF14 4XN, Wales, UK.

出版信息

Curr Opin Pharmacol. 2018 Aug;41:96-103. doi: 10.1016/j.coph.2018.05.005. Epub 2018 May 29.

Abstract

Cancer immunotherapy, focused on harnessing and empowering the immune system against tumours, has transformed modern oncology. One of the most promising avenues in development involves using genetically engineered T-cells to target cancer antigens via specific T-cell receptors (TCRs). TCRs have a naturally low affinity towards cancer-associated antigens, and therefore show scope for improvement. Here we describe approaches to procure TCRs with enhanced affinity and specificity towards cancer, using protein engineering or selection of natural TCRs from unadulterated repertoires. In particular, we discuss novel methods facilitating the targeting of tumour-specific mutations. Finally, we provide a prospective outlook on the potential development of novel, off-the-shelf immunotherapies by leveraging recent advances in genome editing.

摘要

癌症免疫疗法专注于利用和增强免疫系统对抗肿瘤,已经改变了现代肿瘤学。最有前途的发展途径之一是利用基因工程 T 细胞通过特定的 T 细胞受体 (TCR) 靶向癌症抗原。TCR 对癌症相关抗原的亲和力自然较低,因此有改进的空间。在这里,我们描述了使用蛋白质工程或从未受污染的库中选择天然 TCR 来获得对癌症具有增强亲和力和特异性的 TCR 的方法。特别是,我们讨论了促进靶向肿瘤特异性突变的新方法。最后,我们通过利用基因组编辑的最新进展,对利用新型现成免疫疗法的潜在发展进行了前瞻性展望。

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