Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Semin Oncol. 2010 Oct;37(5):473-84. doi: 10.1053/j.seminoncol.2010.09.001.
Cytotoxic T-lymphocyte-associated antigen (CTLA-4), also known as CD152, is a co-inhibitory molecule that functions to regulate T-cell activation. Antibodies that block the interaction of CTLA-4 with its ligands B7.1 and B7.2 can enhance immune responses, including antitumor immunity. Two CTLA-4-blocking antibodies are presently under clinical investigation: ipilimumab and tremelimumab. CTLA-4 blockade has shown promise in treatment of patients with metastatic melanoma, with a recently completed randomized, double-blind phase III trial demonstrating a benefit in overall survival (OS) in the treated population. However, this approach appears to benefit only a subset of patients. Understanding the mechanism(s) of action of CTLA-4 blockade and identifying prognostic immunologic correlates of clinical endpoints to monitor are presently areas of intense investigation. Several immunologic endpoints have been proposed to correlate with clinical activity. This review will focus on the endpoints of immune monitoring described in studies to date and discuss future areas of additional work needed.
细胞毒性 T 淋巴细胞相关抗原 (CTLA-4)，也称为 CD152，是一种共抑制分子，其功能是调节 T 细胞的激活。阻断 CTLA-4 与其配体 B7.1 和 B7.2 相互作用的抗体可以增强免疫反应，包括抗肿瘤免疫。目前有两种 CTLA-4 阻断抗体正在进行临床研究：伊匹单抗和 tremelimumab。CTLA-4 阻断在治疗转移性黑色素瘤患者中显示出前景，最近完成的一项随机、双盲 III 期临床试验表明，治疗人群的总生存期 (OS) 有获益。然而，这种方法似乎只对一部分患者有效。了解 CTLA-4 阻断的作用机制，并确定预测临床终点的免疫预后标志物以进行监测，是目前正在深入研究的领域。已经提出了几种免疫终点来与临床活性相关联。这篇综述将重点介绍迄今为止研究中描述的免疫监测终点，并讨论未来需要进一步开展的工作领域。
