Delivery of transcription factor to cancer cells to reprogram gene expression may represent a novel strategy to augment the production of immune stimulatory cytokines and trigger a more potent antitumor response. In this study, we used a syngeneic mouse tumor model system involving the poorly immunogenic murine B16 tumor to evaluate whether delivery of the interferon regulatory factor 3 (IRF-3) can be used as an immunomodulator. The low immunogenicity of B16 melanoma cells may be due to their deficient cytokine expression, as well as their inefficient MHC-restricted epitope presentation. Gene-modified B16 melanoma cells were selected for their ability to express and to activate the IRF-3 protein. When injected into C57BL/6 mice, tumor growth was inhibited and tumors that developed from these mice had significant infiltration of inflammatory cells. Our observations demonstrated that gene transfer of IRF-3 into B16 melanoma could mediate important antitumor response by restoring both the deficient cytokine profile and the MHC class I protein expression.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.80254 |
| Date | January 2003 |
| Creators | Duguay, Delphine |
| Contributors | Hiscott, John (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Microbiology and Immunology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002031994, proquestno: AAIMQ98623, Theses scanned by UMI/ProQuest. |
Page generated in 0.0023 seconds