Phase I Trial of Intraperitoneal Administration of an Oncolytic Measles Virus Strain Engineered to Express Carcinoembryonic Antigen for Recurrent Ovarian Cancer
| Autor: | Stephen J. Russell, Kah-Whye Peng, Judith S. Kaur, Mark J. Federspiel, C. Robert Stanhope, Lynn C. Hartmann, Paul Haluska, William A. Cliby, Karl C. Podratz, Sean C. Dowdy, Harry J. Long, Evanthia Galanis, Pamela J. Atherton, Gary L. Keeney, Prema P. Peethambaram, Ileana Aderca, Timothy O. Wilson, Paula J. Zollman, Brigitte A. Barrette, Jeff A. Sloan |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Cancer Research medicine.medical_specialty Fever Recombinant Fusion Proteins Gastroenterology Article Measles virus Carcinoembryonic antigen Morbillivirus Internal medicine Chlorocebus aethiops medicine Animals Humans Mononegavirales Vero Cells Fatigue Aged Aged 80 and over Oncolytic Virotherapy Ovarian Neoplasms biology business.industry Cancer Middle Aged biology.organism_classification medicine.disease Abdominal Pain Carcinoembryonic Antigen Oncolytic virus Oncolytic Viruses Treatment Outcome Oncology Immunology biology.protein Female Neoplasm Recurrence Local business Oncofetal antigen Ovarian cancer Injections Intraperitoneal |
| Zdroj: | Cancer Research. 70:875-882 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-09-2762 |
| Popis: | Edmonston vaccine strains of measles virus (MV) have shown significant antitumor activity in preclinical models of ovarian cancer. We engineered MV to express the marker peptide carcinoembryonic antigen (MV-CEA virus) to also permit real-time monitoring of viral gene expression in tumors in the clinical setting. Patients with Taxol and platinum-refractory recurrent ovarian cancer and normal CEA levels were eligible for this phase I trial. Twenty-one patients were treated with MV-CEA i.p. every 4 weeks for up to 6 cycles at seven different dose levels (103–109 TCID50). We observed no dose-limiting toxicity, treatment-induced immunosuppression, development of anti-CEA antibodies, increase in anti-MV antibody titers, or virus shedding in urine or saliva. Dose-dependent CEA elevation in peritoneal fluid and serum was observed. Immunohistochemical analysis of patient tumor specimens revealed overexpression of measles receptor CD46 in 13 of 15 patients. Best objective response was dose-dependent disease stabilization in 14 of 21 patients with a median duration of 92.5 days (range, 54–277 days). Five patients had significant decreases in CA-125 levels. Median survival of patients on study was 12.15 months (range, 1.3–38.4 months), comparing favorably to an expected median survival of 6 months in this patient population. Our findings indicate that i.p. administration of MV-CEA is well tolerated and results in dose-dependent biological activity in a cohort of heavily pretreated recurrent ovarian cancer patients. Cancer Res; 70(3); 875–82 |
| Databáze: | OpenAIRE |
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