Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095–1782, USA.
Semin Oncol. 2010 Oct;37(5):450-4. doi: 10.1053/j.seminoncol.2010.09.010.
Tremelimumab (formerly CP-675,206) is a fully human IgG2 monoclonal antibody tested in patients with cancer, of whom the majority have had metastatic melanoma. Clinical trials using tremelimumab demonstrate that this antibody can induce durable tumor regressions (up to 8 years at this time) in 7% to 10% of patients with metastatic melanoma. These tumor responses are mediated by the intratumoral infiltration of cytotoxic T lymphocytes (CTLs) as demonstrated in patient-derived tumor biopsies. Grade 3 or 4 toxicities in the range of 20% to 25% are mainly inflammatory or autoimmune in nature, which are on-target effects after inhibiting CTLA-4-mediated self-tolerance. The lack of survival advantage in the early analysis of a phase III clinical trial comparing tremelimumab with standard chemotherapy for metastatic melanoma highlights the importance of gaining a better understanding of how this antibody modulates the human immune system and how to better select patients for this mode of therapy.
替西木单抗（曾用名 CP-675,206）是一种已在癌症患者中进行过临床试验的全人源 IgG2 单克隆抗体，其中大多数为转移性黑色素瘤患者。使用替西木单抗的临床试验表明，该抗体可诱导转移性黑色素瘤患者中 7%至 10%的患者出现持久的肿瘤消退（截至目前最长达 8 年）。这些肿瘤反应是由肿瘤内细胞毒性 T 淋巴细胞（CTLs）浸润介导的，这在患者来源的肿瘤活检中得到了证实。3 级或 4 级毒性的发生率为 20%至 25%，主要为炎症或自身免疫性，这是抑制 CTLA-4 介导的自身耐受后的靶向效应。在比较替西木单抗与标准化疗治疗转移性黑色素瘤的 III 期临床试验的早期分析中，没有生存优势，这突出表明需要更好地了解该抗体如何调节人体免疫系统，以及如何更好地选择接受这种治疗模式的患者。
