Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma.
Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma.
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DOI：
10.1158/1078-0432.ccr-11-1595
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发表时间：
2011-11-15
期刊：
影响因子：
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通讯作者：
Drake CG
中科院分区：
文献类型：
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作者：
Lipson EJ;Drake CG
Ipilimumab（MDX-010，Yerkirn; Bristol-Myers Squibb），一种针对CTL抗原4（CTLA-4）的全人单克隆抗体，最近被美国食品和药物管理局（FDA）批准用于治疗转移性黑色素瘤。在早期和晚期试验中，ipilimumab显示出对黑色素瘤的一致活性。例如，在一项随机III期试验中，招募了既往接受过治疗的转移性疾病患者，伊匹单抗（联合或不联合肽疫苗）改善了总生存期：伊匹单抗和伊匹单抗加疫苗组的中位总生存期分别为10.1和10.0个月，而单独疫苗组为6.4个月（风险比，0.68; P ≤ 0.003）。10%-15%的患者发生严重（3-5级）免疫相关不良事件。因此，尽管伊匹单抗给药提供了明显的生存益处，但需要仔细监测患者，有时需要免疫抑制治疗。在这里，我们回顾了导致FDA批准ipilimumab治疗转移性黑色素瘤的作用机制，临床前数据和多项临床试验。
Ipilimumab (MDX-010, Yervoy; Bristol-Myers Squibb), a fully human monoclonal antibody against CTL antigen 4 (CTLA-4), was recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic melanoma. In both early- and late-phase trials, ipilimumab has shown consistent activity against melanoma. For example, in a randomized phase III trial that enrolled patients with previously treated metastatic disease, ipilimumab, with or without a peptide vaccine, improved overall survival: Median overall survival was 10.1 and 10.0 months in the ipilimumab and ipilimumab plus vaccine arms, respectively, versus 6.4 months in the vaccine-alone group (hazard ratio, 0.68; P ≤ 0.003). Serious (grade 3–5) immune-related adverse events occurred in 10% to 15% of patients. Thus, although it provides a clear survival benefit, ipilimumab administration requires careful patient monitoring and sometimes necessitates treatment with immune-suppressive therapy. Here, we review the mechanism of action, preclinical data, and multiple clinical trials that led to FDA approval of ipilimumab for metastatic melanoma.