Park Junsik, Kwon Minsuk, Shin Eui-Cheol
Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
Arch Pharm Res. 2016 Nov;39(11):1577-1587. doi: 10.1007/s12272-016-0850-5. Epub 2016 Oct 21.
During immune responses antigen-specific T cells are regulated by several mechanisms, including through inhibitory receptors and regulatory T cells, to avoid excessive or persistent immune responses. These regulatory mechanisms, which are called 'immune checkpoints', suppress T cell responses, particularly in patients with chronic viral infections and cancer where viral antigens or tumor antigens persist for a long time and contribute to T cell exhaustion. Among these regulatory mechanisms, cytotoxic T lymphocyte associated protein-4 (CTLA-4) and programmed cell death 1 (PD-1) are the most well-known receptors and both have been targeted for drug development. As a result, anti-CTLA-4 and anti-PD-1 (or anti-PD-L1) antibodies were recently developed as immune checkpoint inhibitors for use in cancer treatments. In this review we describe several receptors that function as immunological checkpoints as well as the pharmaceuticals that target them.
在免疫反应过程中,抗原特异性T细胞受到多种机制的调节,包括通过抑制性受体和调节性T细胞,以避免过度或持续的免疫反应。这些调节机制被称为“免疫检查点”,可抑制T细胞反应,尤其是在慢性病毒感染和癌症患者中,病毒抗原或肿瘤抗原长期存在并导致T细胞耗竭。在这些调节机制中,细胞毒性T淋巴细胞相关蛋白4(CTLA-4)和程序性细胞死亡蛋白1(PD-1)是最著名的受体,两者均已成为药物研发的靶点。因此,抗CTLA-4和抗PD-1(或抗PD-L1)抗体最近被开发为免疫检查点抑制剂用于癌症治疗。在本综述中,我们描述了几种作为免疫检查点发挥作用的受体以及针对它们的药物。