Comin-Anduix Begoña, Escuin-Ordinas Helena, Ibarrondo Francisco Javier
Division of Surgical-Oncology, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
Division of Hematology-Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
Onco Targets Ther. 2016 Mar 23;9:1767-76. doi: 10.2147/OTT.S65802. eCollection 2016.
The immune checkpoint therapy is a relatively recent strategy that aims to tweak the immune system to effectively attack cancer cells. The understanding of the immune responses and their regulation at the intracellular level and the development of fully humanized monoclonal antibodies are the pillars of an approach that could elicit durable clinical responses and even remission in some patients with cancer. Most of the immune checkpoints that regulate the T-cell responses (activation and inhibition) operate through proteins present on the cytoplasmic membrane of the immune cells. Therefore, specific antibodies capable of blocking the inhibitory signals should lead to unrestrained immune responses that supersede the inhibitory mechanisms, which are naturally present in the tumor microenviroment. The best-known and most successful targets for immune checkpoint therapy are the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1 coreceptors. Tremelimumab (CP-675,206) is a fully humanized monoclonal antibody specific for cytotoxic T-lymphocyte antigen-4, which has been successfully used to treat patients with metastatic melanoma and some other cancers. Although still a work in progress, the use of tremelimumab as an immune checkpoint therapeutic agent is a promising approach alone or in combination with other anticancer drugs. Here, we review the use of this antibody in a number of clinical trials against solid tumors.
免疫检查点疗法是一种相对较新的策略，旨在调整免疫系统以有效攻击癌细胞。对细胞内水平的免疫反应及其调节的理解以及完全人源化单克隆抗体的开发是一种能够在一些癌症患者中引发持久临床反应甚至缓解的方法的支柱。大多数调节T细胞反应（激活和抑制）的免疫检查点通过免疫细胞质膜上存在的蛋白质发挥作用。因此，能够阻断抑制信号的特异性抗体应能导致不受抑制的免疫反应，从而取代肿瘤微环境中天然存在的抑制机制。免疫检查点疗法最著名且最成功的靶点是细胞毒性T淋巴细胞抗原4和程序性细胞死亡蛋白1共受体。曲美木单抗（CP-675,206）是一种针对细胞毒性T淋巴细胞抗原4的完全人源化单克隆抗体，已成功用于治疗转移性黑色素瘤患者和其他一些癌症。尽管仍在进行中，但曲美木单抗作为一种免疫检查点治疗药物单独使用或与其他抗癌药物联合使用是一种有前景的方法。在此，我们综述了该抗体在一些针对实体瘤的临床试验中的应用。
