改良安卡拉痘苗病毒-5T4作为晚期人类癌症特异性免疫疗法的研发。
Development of modified vaccinia Ankara-5T4 as specific immunotherapy for advanced human cancer.
作者信息
Tykodi Scott S, Thompson John A
机构信息
Seattle Cancer Care Alliance, 825 Eastlake Avenue East, Mailstop G4-830, Seattle, WA 98109-1023, USA.
出版信息
Expert Opin Biol Ther. 2008 Dec;8(12):1947-53. doi: 10.1517/14712590802567298.
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.
背景
肿瘤相关抗原5T4在大多数人类癌症中高表达，而在正常组织中表达有限。一种表达该抗原的重组痘病毒载体，即改良安卡拉痘苗病毒（MVA）-5T4，已作为癌症疫苗进行了测试。
目的
在晚期结直肠癌、肾细胞癌（RCC）或激素难治性前列腺癌患者中，已对MVA-5T4作为单一药物治疗以及与标准化疗、生物治疗或靶向治疗联合使用进行了研究。
方法
本综述总结了已发表的手稿、会议摘要或与临床试验或MVA-5T4相关网站上报道的MVA-5T4临床研究数据。
结果/结论：用MVA-5T4进行疫苗接种耐受性良好，并且在大多数接受治疗的患者中引发5T4特异性体液和/或细胞反应。对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、安慰剂对照试验旨在证实用MVA-5T4进行疫苗接种与晚期RCC患者生存率之间的正相关。
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