Callahan Margaret K, Wolchok Jedd D
Melanoma and Immunotherapeutics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; Weill Medical College of Cornell University, New York, NY.
Melanoma and Immunotherapeutics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; Weill Medical College of Cornell University, New York, NY; Ludwig Center for Cancer Immunotherapy, New York, NY.
Semin Oncol. 2015 Aug;42(4):573-86. doi: 10.1053/j.seminoncol.2015.05.008. Epub 2015 Jun 3.
Evidence that the immune system can recognize, and in some cases control or even eliminate tumors, is increasingly clear. Encouraging T-cell activation by blocking regulatory or "checkpoint" molecules is a potent way to amplify anti-tumor immune responses. Successfully exploiting this concept, a new class of anti-cancer therapies, "checkpoint-blocking" antibodies has emerged. The first checkpoint-blocking antibody to enter the clinic was ipilimumab, an antibody that blocks the co-inhibitory receptor cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Herein we review the clinical development of CTLA-4 blocking antibodies, including preclinical studies, clinical activity, toxicities, the search for potential biomarkers, and early clinical experience with combinations.
免疫系统能够识别肿瘤，并且在某些情况下能够控制甚至消除肿瘤，这方面的证据越来越明确。通过阻断调节性或“检查点”分子来促进T细胞活化是增强抗肿瘤免疫反应的有效方法。成功利用这一概念，一类新型抗癌疗法——“检查点阻断”抗体应运而生。首个进入临床的检查点阻断抗体是伊匹单抗，它是一种阻断共抑制受体细胞毒性T淋巴细胞相关抗原4（CTLA-4）的抗体。在此，我们综述CTLA-4阻断抗体的临床研发情况，包括临床前研究、临床活性、毒性、潜在生物标志物的探索以及联合用药的早期临床经验。
