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Development of modified vaccinia Ankara-5T4 as specific immunotherapy for advanced human cancer.

机译:改良牛痘安卡拉5T4作为晚期人类癌症的特异性免疫疗法的开发。

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BACKGROUND: The tumor-associated antigen 5T4 is expressed on a high percentage of human carcinomas and has limited expression in normal tissues. A recombinant pox virus vector expressing this antigen, modified vaccinia Ankara (MVA)-5T4, has been tested as a cancer vaccine. OBJECTIVE: Treatment with MVA-5T4 has been studied both as a single agent and in combination with standard chemo-, biologic- or targeted-therapies in patients with advanced colorectal cancer, renal cell carcinoma (RCC) or hormone-refractory prostate cancer. METHODS: This review summarizes data from clinical studies with MVA-5T4 reported in published manuscripts, meeting abstracts or posted on websites relevant to clinical trials or MVA-5T4. RESULTS/CONCLUSION: Vaccination with MVA-5T4 is well tolerated and elicits 5T4-specific humoral and/or cellular responses in most of the treated patients. Retrospective analyses of Phase II studies have suggested a positive association between immune responses to 5T4 and favorable clinical outcomes. A continuing Phase III, double-blind, placebo-controlled trial seeks to confirm a positive association between vaccination with MVA-5T4 and survival in patients with advanced RCC.
机译:背景:肿瘤相关抗原5T4在高比例的人类癌症中表达,在正常组织中的表达有限。表达该抗原的重组痘病毒载体,经修饰的牛痘安卡拉(MVA)-5T4,已作为癌症疫苗进行了测试。目的:已经研究了以MVA-5T4作为单一药物以及与标准的化学,生物或靶向疗法联合治疗晚期大肠癌,肾细胞癌(RCC)或激素难治性前列腺癌的方法。方法:本综述总结了来自MVA-5T4的临床研究数据,这些数据在已发表的手稿,会议摘要或与临床试验或MVA-5T4相关的网站上发布。结果/结论:对MVA-5T4的疫苗接种耐受性良好,并且在大多数接受治疗的患者中引起5T4特异性体液和/或细胞反应。 II期研究的回顾性分析表明,对5T4的免疫反应与良好的临床结果之间存在正相关。一项正在进行的III期,双盲,安慰剂对照的III期临床试验旨在确认MVA-5T4疫苗接种与晚期RCC患者的生存之间存在正相关关系。

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