当前位置: X-MOL 学术Annu. Rev. Cancer Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Is There a Clinical Future for IDO1 Inhibitors After the Failure of Epacadostat in Melanoma?
Annual Review of Cancer Biology ( IF 4.7 ) Pub Date : 2020-03-09 , DOI: 10.1146/annurev-cancerbio-030419-033635
Benoit J. Van den Eynde 1, 2, 3 , Nicolas van Baren 2 , Jean-François Baurain 4, 5
Affiliation  

Indoleamine-2,3 dioxygenase 1 (IDO1) contributes to tumor immunosuppression by enzymatically degrading tryptophan, which is required for T cell activity, and producing kynurenine. Small-molecule inhibitors, such as epacadostat, have been developed to block IDO1 activity. In preclinical models, they can restore antitumoral T cell immunity and synergize with immune checkpoint inhibitors or cancer vaccines. Based on encouraging clinical results in early phase trials, a randomized phase III study (ECHO-301/KN-252) was launched in metastatic melanoma to test the benefit of adding epacadostat to the reference pembrolizumab therapy. The result was negative. We briefly review the clinical trials that investigated epacadostat in cancer patients and discuss possible explanations for this negative result. We end by suggesting paths to resume clinical development of compounds targeting the IDO1 pathway, which in our view remains an attractive target for cancer immunotherapy.

中文翻译:


Epacadostat在黑色素瘤中失败后,IDO1抑制剂的临床前景如何?

吲哚胺-2,3双加氧酶1(IDO1)通过酶促降解T细胞活性所需的色氨酸和产生犬尿氨酸来促进肿瘤的免疫抑制。已经开发出小分子抑制剂,例如依帕卡司他,以阻断IDO1活性。在临床前模型中,它们可以恢复抗肿瘤T细胞免疫力,并与免疫检查点抑制剂或癌症疫苗协同作用。基于早期试验中令人鼓舞的临床结果,一项针对转移性黑色素瘤的随机III期研究(ECHO-301 / KN-252)开展了试验,以测试将依帕多司他加入参比派姆单抗治疗的益处。结果为阴性。我们简要回顾了研究依帕多司他在癌症患者中的临床试验,并讨论了该阴性结果的可能解释。

更新日期:2020-03-09
down
wechat
bug