Pharmacokinetics of oncolytic measles virotherapy: eventual equilibrium between virus and tumor in an ovarian cancer xenograft model
| Autor: | Mary Harvey, Mark J. Federspiel, Rae Myers, Kah-Whye Peng, Diane Soeffker, Suzanne Greiner, Elizabeth M. Hadac, Anderson Bd, Stephen J. Russell |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Dose-Response Relationship Immunologic Measles Virus Measles virus Mice Carcinoembryonic antigen Pharmacokinetics medicine Tumor Cells Cultured Animals Humans Virotherapy Molecular Biology Oncolytic Virotherapy Ovarian Neoplasms biology business.industry biology.organism_classification medicine.disease Xenograft Model Antitumor Assays Oncolytic virus Carcinoembryonic Antigen Tumor Burden Immunology Cancer research biology.protein Molecular Medicine Female Ovarian cancer business |
| Zdroj: | Cancer gene therapy. 13(8) |
| ISSN: | 0929-1903 |
| Popis: | Because of their ability to replicate, the dose-response relationships of oncolytic viruses cannot easily be predicted. To better understand the pharmacokinetics of virotherapy in relation to viral dose and schedule, we administered MV-CEA intraperitoneally in an orthotopic mouse model of ovarian cancer. MV-CEA is an attenuated oncolytic measles virus engineered to express soluble human carcinoembryonic antigen (CEA), and the virus is currently undergoing phase I clinical testing in patients with ovarian cancer. Plasma CEA levels correlate with numbers of virus-infected tumor cells at a given time, and were used as a surrogate to monitor the profiles of viral gene expression over time. The antineoplastic activity of single- or multiple-dose MV-CEA was apparent over a wide range of virus doses (10(3)-10(8) TCID(50)), with little reduction in observed antitumor efficacy, even at the lowest tested dose. However, analysis of CEA profiles of treated mice was highly informative, illustrating the variability in virus kinetics at different dose levels. The highest doses of virus were associated with higher initial levels of tumor cell killing, but the final outcome of MV-CEA therapy at all dose levels was a partial equilibrium between virus and tumor, resulting in significant slowing of tumor growth and enhanced survival of the mice. |
| Databáze: | OpenAIRE |
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