51. Harnessing oncolytic virus-mediated antitumor immunity in an infected cell vaccine.
- Author
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Lemay CG, Rintoul JL, Kus A, Paterson JM, Garcia V, Falls TJ, Ferreira L, Bridle BW, Conrad DP, Tang VA, Diallo JS, Arulanandam R, Le Boeuf F, Garson K, Vanderhyden BC, Stojdl DF, Lichty BD, Atkins HL, Parato KA, Bell JC, and Auer RC
- Subjects
- Animals, Antigens, Neoplasm genetics, Antigens, Neoplasm immunology, Cancer Vaccines administration & dosage, Cell Line, Tumor, Chlorocebus aethiops, Female, Genetic Therapy methods, Granulocyte-Macrophage Colony-Stimulating Factor immunology, Humans, Immunization, Interferon-gamma biosynthesis, Interferon-gamma immunology, Killer Cells, Natural immunology, Killer Cells, Natural metabolism, Melanoma, Experimental immunology, Mice, Mice, Inbred C57BL, Oncolytic Virotherapy methods, Oncolytic Viruses genetics, Oncolytic Viruses immunology, Skin Neoplasms immunology, T-Lymphocytes immunology, T-Lymphocytes metabolism, Vero Cells, Vesiculovirus genetics, Virus Replication, Cancer Vaccines immunology, Melanoma, Experimental prevention & control, Melanoma, Experimental therapy, Skin Neoplasms prevention & control, Skin Neoplasms therapy, Vesiculovirus immunology
- Abstract
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.
- Published
- 2012
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