Simsek Melih, Tekin Salim Basol, Bilici Mehmet
Department of Medical Oncology, Atatürk University School of Medicine, Erzurum, Turkey.
Eurasian J Med. 2019 Feb;51(1):90-94. doi: 10.5152/eurasianjmed.2018.18194. Epub 2018 Nov 30.
Immune checkpoint inhibitors (ICI) are monoclonal antibodies targeting cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1), or PD-1 ligand (PD-L1). ICI are approved for the treatment of malign melanoma, non-small cell lung cancer, classical Hodgkin lymphoma, head and neck squamous cell carcinoma, urothelial carcinoma, and renal cell carcinoma. They can lead to long-term anti-tumor responses by deactivating the brake mechanism in the immune system. Ipilimumab, tremelimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab are examples of ICI. CTLA-4 is a brake mechanism in immune response. Ipilimumab and tremelimumab are antibodies against CTLA-4. PD-1 is another important immune checkpoint co-inhibitor receptor that is expressed by activated T cells in the peripheral tissue. As a result of blockage of the PD-1/PD-L1 pathway, local tumor-specific immune response augments, and long-term tumor control can be achieved. In recent years, ICI are approved for the treatment of various malignities. They may be responsible for specific toxicities called immune-related adverse events (irAEs). irAEs are a consequence infiltration of normal tissues by activated T lymphocytes that are responsible for autoimmunity. Corticosteroids and anti-tumor necrosis factor agents, such as infliximab and mycophenolate mofetil, are effective in the treatment of irAEs. Immune checkpoint inhibition with monoclonal antibodies against CTLA-4 and/or PD-1/PD-L1 by single agent or combination treatments became a new option in various solid tumors. However, ICI have unique adverse events, and these adverse events should be considered in any new onset clinical situation and should be managed properly. Future prospective randomized clinical trials will clarify recent questions.
免疫检查点抑制剂(ICI)是靶向细胞毒性T淋巴细胞相关抗原4(CTLA-4)、程序性细胞死亡蛋白1(PD-1)或PD-1配体(PD-L1)的单克隆抗体。ICI已被批准用于治疗恶性黑色素瘤、非小细胞肺癌、经典型霍奇金淋巴瘤、头颈部鳞状细胞癌、尿路上皮癌和肾细胞癌。它们可通过解除免疫系统中的制动机制来引发长期抗肿瘤反应。伊匹木单抗、曲美木单抗、帕博利珠单抗、纳武利尤单抗、阿特珠单抗、度伐利尤单抗和阿维鲁单抗均为ICI的实例。CTLA-4是免疫反应中的一种制动机制。伊匹木单抗和曲美木单抗是抗CTLA-4抗体。PD-1是另一种重要的免疫检查点共抑制受体,在外周组织中由活化的T细胞表达。由于PD-1/PD-L1通路受阻,局部肿瘤特异性免疫反应增强,从而可实现长期肿瘤控制。近年来,ICI已被批准用于治疗各种恶性肿瘤。它们可能会引发称为免疫相关不良事件(irAE)的特定毒性反应。irAE是由负责自身免疫性的活化T淋巴细胞浸润正常组织所致。皮质类固醇和抗肿瘤坏死因子药物,如英夫利昔单抗和霉酚酸酯,对irAE的治疗有效。通过单药或联合治疗使用抗CTLA-4和/或PD-1/PD-L1的单克隆抗体进行免疫检查点抑制已成为各种实体瘤的一种新选择。然而,ICI有独特的不良事件,在任何新出现的临床情况中都应考虑这些不良事件并进行妥善处理。未来的前瞻性随机临床试验将阐明近期的问题。