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.
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