title: Harnessing oncolytic virus-mediated antitumor immunity in an infected cell vaccine.
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.
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Chantal G
authors: CG
authors: Lemay
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Julia L
authors: JL
authors: Rintoul
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Agnieszka
authors: A
authors: Kus
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Jennifer M
authors: JM
authors: Paterson
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Vanessa
authors: V
authors: Garcia
authors: Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Theresa J
authors: TJ
authors: Falls
authors: Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Lisa
authors: L
authors: Ferreira
authors: Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada.
authors: Byram W
authors: BW
authors: Bridle
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: David P
authors: DP
authors: Conrad
authors: Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Vera A
authors: VA
authors: Tang
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Jean-Simon
authors: JS
authors: Diallo
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Rozanne
authors: R
authors: Arulanandam
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Fabrice
authors: F
authors: Le Boeuf
authors: Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Kenneth
authors: K
authors: Garson
authors: Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Barbara C
authors: BC
authors: Vanderhyden
authors: Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: David F
authors: DF
authors: Stojdl
authors: Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada.
authors: Brian D
authors: BD
authors: Lichty
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Harold L
authors: HL
authors: Atkins
authors: Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Kelley A
authors: KA
authors: Parato
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada. Electronic address: jbell@ohri.ca.
authors: John C
authors: JC
authors: Bell
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Centre for Innovative Cancer Therapeutics, Ottawa, Ontario, Canada.
authors: Rebecca C
authors: RC
authors: Auer
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014709:Vero Cells; D018116:Vesiculovirus / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor