title: The Effect of Vector Silencing during Picornavirus Vaccination against Experimental Melanoma and Glioma.
abstract: Virus vector-based vaccination against tumor-specific antigens remains a promising therapeutic approach to overcome the immune suppressive tumor microenvironment. However, the extent that the desired CD8 T cell response against the targeted tumor antigen is impacted by the CD8 T cell response against the virus vector is unclear. To address this question, we used picornavirus vaccination with Theiler's murine encephalomyelitis virus (TMEV) as our vector against tumor-expressed ovalbumin (OVA257-264) antigen in both the B16-OVA murine melanoma and GL261-quad cassette murine glioma models. Prior to vaccination, we employed vector silencing to inhibit the CD8 T cell response against the immunodominant TMEV antigen, VP2121-130. We then monitored the resulting effect on the CD8 T cell response against the targeted tumor-specific antigen, ovalbumin. We demonstrate that employing vector silencing in the context of B16-OVA melanoma does not reduce tumor burden or improve survival, while TMEV-OVA vaccination without vector silencing controls tumor burden. Meanwhile, employing vector silencing during picornavirus vaccination against the GL261-quad cassette glioma resulted in a lower frequency of tumor antigen-specific CD8 T cells. The results of this study are relevant to antigen-specific immunotherapy, in that the virus vector-specific CD8 T cell response is not competing with tumor antigen-specific CD8 T cells. Furthermore, vector silencing may have the adverse consequence of reducing the tumor antigen-specific CD8 T cell response, as demonstrated by our findings in the GL261-quad cassette model.
authors: Department of Immunology, Mayo Clinic, Rochester, MN, United States of America.|Mayo Graduate School, Mayo Clinic, Rochester, MN, United States of America.
authors: Courtney S
authors: http://orcid.org/0000-0001-9674-3826
authors: CS
authors: Malo
authors: Mayo Graduate School, Mayo Clinic, Rochester, MN, United States of America.|Neurobiology of Disease Graduate Program, Mayo Clinic, Rochester, MN, United States of America.
authors: Danielle N
authors: DN
authors: Renner
authors: Department of Immunology, Mayo Clinic, Rochester, MN, United States of America.|Mayo Graduate School, Mayo Clinic, Rochester, MN, United States of America.
authors: April M
authors: AM
authors: Huseby Kelcher
authors: Department of Immunology, Mayo Clinic, Rochester, MN, United States of America.
authors: Fang
authors: F
authors: Jin
authors: Department of Immunology, Mayo Clinic, Rochester, MN, United States of America.
authors: Michael J
authors: MJ
authors: Hansen
authors: Department of Immunology, Mayo Clinic, Rochester, MN, United States of America.
authors: Kevin D
authors: KD
authors: Pavelko
authors: Department of Immunology, Mayo Clinic, Rochester, MN, United States of America.|Department of Neurology, Mayo Clinic, Rochester, MN, United States of America.
authors: Aaron J
authors: AJ
authors: Johnson
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D005910:Glioma / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology*; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology*; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010849:Picornaviridae / Q000235:genetics / Q000276:immunology; D017945:Theilovirus / Q000235:genetics / Q000276:immunology*; D047368:Tumor Burden / Q000235:genetics / Q000276:immunology; D014611:Vaccination / Q000379:methods*
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D010047:Ovalbumin