Measles Virus Therapy for Ovarian Cancer

麻疹病毒治疗卵巢癌

• 批准号: 6691565
• 负责人: Evanthia Galanis
• 金额: $ 26.94万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6691565
• 关键词: antineoplastics; attenuated microorganism; biomarker; carcinoembryonal antigen; cellular immunity; clinical research; clinical trial phase I; dosage; female; gene expression; human subject; human therapy evaluation; humoral immunity; intraperitoneal injections; measles virus; neoplasm /cancer relapse /recurrence; neoplasm /cancer therapy; neoplastic cell; ovary neoplasms; patient oriented research; serology /serodiagnosis; virus cytopathogenic effect; virus genetics; virus load; virus replication; women's health

Ovarian cancer is the most common cause of gynecologic cancer deaths in the US and it is responsible for more than 14,000 deaths each year. Recurrent disease remains incurable and has a dismal prognosis. Novel therapeutic agents are urgently needed. MV-CEA is a novel viral agent deriving from the Edmonston's vaccine strain of measles virus, which was developed at the Molecular Medicine Program of the Mayo Clinic Cancer Center. The virus has been engineered to produce CEA, that serves as a trackable marker of viral gene expression and can be used for monitoring of viral therapy in vivo. In preclinical work we have demonstrated significant antitumor potential of the virus, both in vitro and in vivo against ovarian cancer animal models, while CEA levels in the serum represented a very helpful correlate of viral gene expression. This proposal includes two novel concepts: use of an attenuated measles virus of the Edmonston's vaccine lineage as an antitumor agent against ovarian cancer and use of a novel tracking system that could significantly improve our ability to monitor virotherapy trials. Our hypothesis is that MV-CEA will be a safe and effective agent for treatment of recurrent ovarian cancer. We also hypothesize that detection of CEA in patients' serum can serve as an effective means of following viral gene expression and could allow dose optimization in future applications of this agent. Therefore, we propose to conduct a phase I trial of MV-CEA in patients with recurrent ovarian cancer with the following objectives: a) to assess the safety of intraperitoneal administration of MV-CEA in patients with recurrent ovarian cancer and to determine the maximum tolerated dose of MV-CEA in this setting; b) to characterize the profile of viral gene expression at each dose level as manifested by the serum CEA concentrations and to assess viremia, viral replication, and measles virus shedding and persistence; c) to determine humoral and cellular immune response to the injected virus and correlate it with toxicity, viremia, CEA levels, and response; and d) to assess in a preliminary fashion anti-tumor efficacy of this approach.

卵巢癌是美国妇科癌症死亡的最常见原因，每年造成14,000多人死亡。复发性疾病仍然无法治愈，预后却令人沮丧。迫切需要新颖的治疗剂。 MV-CEA是一种新型的病毒剂，它源自Edmonston的麻疹病毒疫苗菌株，该病毒是在Mayo临床癌症中心的分子医学计划中开发的。该病毒已被设计为产生CEA，可作为病毒基因表达的可追踪标记，可用于监测体内病毒疗法。在临床前工作中，我们在体外和体内都表现出了该病毒的显着抗肿瘤潜力 卵巢癌动物模型，而血清中的CEA水平代表了病毒基因表达的非常有用的相关性。 该提案包括两个新的概念：使用Edmonston疫苗谱系的衰减麻疹病毒作为抗卵巢癌的抗肿瘤剂，并使用新型的跟踪系统，该系统可以显着提高我们监测病毒疗法试验的能力。我们的假设是MV-CEA将是治疗复发性卵巢癌的安全有效药物。我们还假设患者血清中CEA的检测可以作为遵循病毒基因表达的有效手段，并且可以在该药物的未来应用中优化剂量。因此，我们建议对复发性卵巢癌患者进行MV-CEA的I期试验，并具有以下目标：a）评估腹膜内对复发性卵巢癌患者的MV-CEA给药的安全性，并确定在这种情况下MV-CEA的最大耐受剂量； b）表征病毒基因的轮廓 在每个剂量水平上的表达由血清CEA浓度表现出来，并评估病毒血症，病毒复制和麻疹病毒脱落和持久性； c）确定对注射病毒的体液和细胞免疫反应，并将其与毒性，病毒血症，CEA水平和反应相关联； d）以这种方法的初步抗肿瘤功效进行评估。