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| Content Provider | PubMed Central |
|---|---|
| Author | Willmon, Candice L. Saloura, Vassiliki Fridlender, Zvi G. Wongthida, Phonphimon Diaz, Rosa Maria Thompson, Jill Kottke, Timothy Federspiel, Mark Barber, Glen Albelda, Steven M. Vile, Richard G. |
| Abstract | Our pre-clinical and clinical trials using a replication-defective adenoviral vector expressing IFN-β have shown promising results for the treatment of malignant mesothelioma. Based on the hypotheses that a replication-competent Vesicular Stomatitis Virus (VSV) oncolytic vector would transduce more tumor cells in vivo, that co-expression of the immunostimulatory IFN-β gene would enhance the immune-based effector mechanisms associated both with regression of mesotheliomas and with VSV-mediated virotherapy, and that virus-derived IFN-β would add further safety to the VSV platform, we tested the use of IFN-β as a therapeutic transgene expressed from VSV as a novel treatment for mesothelioma. VSV-IFN-β showed significant therapy against AB12 murine mesotheliomas in the context of both local and loco-regional viral delivery. Biologically active IFN-β expressed from VSV added significantly to therapy compared to VSV alone, dependent in part upon host CD8+ T-cell responses. Immune monitoring suggested that these anti-tumor T-cell responses may be due to a generalised T-cell activation rather than the priming of tumor antigen-specific T-cell responses. Finally, IFN-β also added considerable extra safety to the virus by providing protection from off-target viral replication in non-tumor tissues and protected SCID mice from developing lethal neurotoxicity. The enhanced therapeutic index provided by the addition of IFN-β to VSV therefore provides a powerful justification for the development of this virus for future clinical trials. |
| Related Links | http://dx.doi.org/10.1158/0008-5472.can-09-1013 |
| Ending Page | 7720 |
| Page Count | 8 |
| Starting Page | 7713 |
| File Format | |
| ISSN | 00085472 |
| e-ISSN | 15387445 |
| Journal | Cancer research |
| Issue Number | 19 |
| Volume Number | 69 |
| Language | English |
| Publisher Date | 2009-10-01 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Oncology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
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