Harnessing Oncolytic Virus-mediated Antitumor Immunity in an Infected Cell Vaccine
| Autor: | David F. Stojdl, Jennifer M Paterson, John C. Bell, Fabrice Le Boeuf, Agnieszka Kus, Byram W. Bridle, Rozanne Arulanandam, Brian D. Lichty, Rebecca C. Auer, David P. Conrad, Harold L. Atkins, Julia L Rintoul, Vera A Tang, Jean-Simon Diallo, Kelley Parato, Vanessa Garcia, Kenneth Garson, Lisa Ferreira, Chantal G Lemay, Barbara C. Vanderhyden, Theresa Falls |
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| Rok vydání: | 2012 |
| Předmět: |
Skin Neoplasms
T-Lymphocytes viruses Melanoma Experimental Biology Virus Replication Cancer Vaccines Virus Interferon-gamma Mice 03 medical and health sciences 0302 clinical medicine Immune system Antigen Antigens Neoplasm Cell Line Tumor Chlorocebus aethiops Drug Discovery Genetics Animals Humans Vero Cells Molecular Biology Tropism 030304 developmental biology Oncolytic Virotherapy Pharmacology 0303 health sciences Granulocyte-Macrophage Colony-Stimulating Factor Genetic Therapy Vesiculovirus Virology Tumor antigen 3. Good health Oncolytic virus Killer Cells Natural Mice Inbred C57BL Oncolytic Viruses Viral replication 13. Climate action 030220 oncology & carcinogenesis Cancer cell Molecular Medicine Original Article Female Immunization |
| Zdroj: | Molecular Therapy. 20(9):1791-1799 |
| ISSN: | 1525-0016 |
| DOI: | 10.1038/mt.2012.128 |
| Popis: | Treatment of permissive tumors with the oncolytic virus (OV) VSV-Δ51 leads to a robust antitumor T-cell response, which contributes to efficacy; however, many tumors are not permissive to in vivo treatment with VSV-Δ51. In an attempt to channel the immune stimulatory properties of VSV-Δ51 and broaden the scope of tumors that can be treated by an OV, we have developed a potent oncolytic vaccine platform, consisting of tumor cells infected with VSV-Δ51. We demonstrate that prophylactic immunization with this infected cell vaccine (ICV) protected mice from subsequent tumor challenge, and expression of granulocyte-monocyte colony stimulating factor (GM-CSF) by the virus (VSVgm-ICV) increased efficacy. Immunization with VSVgm-ICV in the VSV-resistant B16-F10 model induced maturation of dendritic and natural killer (NK) cell populations. The challenge tumor is rapidly infiltrated by a large number of interferon γ (IFNγ)-producing T and NK cells. Finally, we demonstrate that this approach is robust enough to control the growth of established tumors. This strategy is broadly applicable because of VSV's extremely broad tropism, allowing nearly all cell types to be infected at high multiplicities of infection in vitro, where the virus replication kinetics outpace the cellular IFN response. It is also personalized to the unique tumor antigen(s) displayed by the cancer cell. |
| Databáze: | OpenAIRE |
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