靶向吲哚胺2,3-双加氧酶(IDO)的肿瘤免疫治疗小分子抑制剂研发进展

doi:10.3969/j.issn.1000-5641.2018.03.021

摘要/Abstract

摘要： 在肿瘤的发生发展的过程中，癌细胞可以通过多种免疫逃脱机制避免机体免疫系统的清除.在正常人体内，吲哚胺2，3-双加氧酶（Indoleamine 2，3-dioxygenase，IDO）是一种存在于免疫细胞内可以催化色氨酸通过犬尿氨酸通路代谢的酶，肿瘤的发生发展引发的炎症会诱导肿瘤微环境中的树突状细胞和肿瘤细胞持续高表达IDO，使肿瘤微环境中的色氨酸持续消耗，抑制对色氨酸敏感的T细胞的功能活性，进而抑制肿瘤组织局部的免疫活性，最终导致癌细胞逃脱免疫细胞的杀伤.抑制IDO的活性及其表达可以有效激活免疫系统对肿瘤的杀伤作用，因此，IDO成为了肿瘤免疫治疗的一个新靶点，目前针对IDO的抑制剂已经有Epacadostat、Indoximod、GDC-0919和BMS-986205进入临床试验阶段，并有望作为肿瘤分子免疫治疗药物上市用于癌症的治疗，同时，新型IDO抑制剂PF-06840003和RG70099等也在不断地被研发出来.现就IDO对于肿瘤免疫的调节机制以及开发IDO抑制剂成为肿瘤免疫治疗新药的研究进展进行综述.

关键词: 吲哚胺2, 3-双加氧酶, IDO抑制剂, 免疫调节, 癌症治疗

Abstract: In the development of cancer, cancer cells can employ a number of mechanisms to escape detection by the immune system. Indoleamine 2, 3-dioxygenase (IDO) is a type of enzyme in immune cells, which catalyzes the metabolism of tryptophan through the kynurenine pathway. Inflammation induced by cancer development can result in overexpression of IDO in protuberance cells and tumor cells in the tumor microenvironment,causing sustained consumption of tryptophan, inhibition of tryptophan-sensitive T cells functional activity, and a decrease in local immune activity in tumor tissues. Inhibition of IDO activity and its expression could effectively activate the immune system to kill tumor cells. Therefore, IDO has become a new target in cancer immunotherapy. Currently, four IDO inhibitors, namely Epacadostat, Indoximod, GDC-0919 and BMS-986205, are in the clinical research stage as potential new anti-cancer molecule immunotherapy drugs. At the same time, new IDO inhibitors such as PF-06840003 and RG70099 are also being investigated. In this article, the pogress of research on IDO and the development of IDO inhibitors as a new anti-cancer drug for tumor immunotherapy is reviewed.

Key words: indoleamine 2,3-dioxygenase, IDO inhibitors, immune system regulation, cancer treatment

中图分类号:

Q948

陈瑞, 方艳芬, 章雄文. 靶向吲哚胺2,3-双加氧酶(IDO)的肿瘤免疫治疗小分子抑制剂研发进展[J]. 华东师范大学学报(自然科学版), 2018, 2018(3): 196-211.

CHEN Rui, FANG Yan-fen, ZHANG Xiong-wen. Progress in development of small molecule inhibitors targeting indoleamine 2,3-dioxygenase[J]. Journal of East China Normal University(Natural Sc, 2018, 2018(3): 196-211.

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