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Cancer immunotherapy harnessing γδ T cells and programmed death-1.
Immunological Reviews ( IF 8.7 ) Pub Date : 2020-09-05 , DOI: 10.1111/imr.12917
Yoshimasa Tanaka 1
Affiliation  

Cancer immunotherapy has received increasing attention since the success of CTLA‐4 and programmed death‐1 (PD‐1) immune checkpoint inhibitors and CAR‐T cells. One of the most promising next‐generation cancer treatments is adoptive transfer of immune effector cells. Developing an efficacious adoptive transfer therapy requires growing large numbers of highly purified immune effector cells in a short period of time. γδ T cells can be effectively expanded using synthetic antigens such as pyrophosphomonoesters and nitrogen‐containing bisphosphonates (N‐BPs). Pyrophosphomonoester antigens, initially identified in mycobacterial extracts, were used for this purpose in the early years of the development of γδ T cell‐based therapy. GMP‐grade N‐BPs, which are now commercially available, are used in many clinical trials worldwide. In order to develop N‐BPs for cancer immunotherapy, N‐BP prodrugs have been synthesized; among these, tetrakis‐pivaloyloxymethyl 2‐(thiazole‐2‐ylamino)ethylidene‐1,1‐bisphosphonate (PTA) is the most potent compound for stimulating γδ T cells. The activated γδ T cells express high levels of PD‐1, suggesting the potential for a combination therapy harnessing γδ T cells and PD‐1 immune checkpoint inhibitors. In addition, the functions of γδ T cells can be modified by IL‐18. Collectively, the recent findings show that γδ T cells are one of the most promising immune effector subsets for the development of novel cancer immunotherapy.

中文翻译:

利用 γδ T 细胞和程序性死亡的癌症免疫疗法-1。

自从 CTLA-4 和程序性死亡 1 (PD-1) 免疫检查点抑制剂和 CAR-T 细胞的成功以来,癌症免疫疗法受到越来越多的关注。最有希望的下一代癌症治疗方法之一是免疫效应细胞的过继转移。开发有效的过继转移疗法需要在短时间内培养大量高度纯化的免疫效应细胞。γδ T 细胞可以使用合成抗原有效扩增,如焦磷酸单酯和含氮双膦酸盐 (N-BP)。最初在分枝杆菌提取物中鉴定的焦磷酸单酯抗原在基于 γδ T 细胞疗法发展的早期被用于此目的。GMP 级 N-BP 现已上市,已用于全球许多临床试验。为了开发用于癌症免疫治疗的 N-BP,已经合成了 N-BP 前药;其中,四-新戊酰氧基甲基 2-(噻唑-2-基氨基)亚乙基-1,1-二膦酸酯 (PTA) 是刺激 γδ T 细胞最有效的化合物。活化的 γδ T 细胞表达高水平的 PD-1,表明利用 γδ T 细胞和 PD-1 免疫检查点抑制剂进行联合治疗的潜力。此外,IL-18 可以改变 γδ T 细胞的功能。总的来说,最近的研究结果表明,γδ T 细胞是开发新型癌症免疫疗法最有希望的免疫效应子集之一。活化的 γδ T 细胞表达高水平的 PD-1,表明利用 γδ T 细胞和 PD-1 免疫检查点抑制剂进行联合治疗的潜力。此外,IL-18 可以改变 γδ T 细胞的功能。总的来说,最近的研究结果表明,γδ T 细胞是开发新型癌症免疫疗法最有希望的免疫效应子集之一。活化的 γδ T 细胞表达高水平的 PD-1,表明利用 γδ T 细胞和 PD-1 免疫检查点抑制剂进行联合治疗的潜力。此外,IL-18 可以改变 γδ T 细胞的功能。总的来说,最近的研究结果表明,γδ T 细胞是开发新型癌症免疫疗法最有希望的免疫效应子集之一。
更新日期:2020-09-05
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