The Effect of Vector Silencing during Picornavirus Vaccination against Experimental Melanoma and Glioma

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 agains...

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Bibliographic Details
Published in:PloS one 2016-08, Vol.11 (8), p.e0162064-e0162064
Main Authors: Malo, Courtney S, Renner, Danielle N, Huseby Kelcher, April M, Jin, Fang, Hansen, Michael J, Pavelko, Kevin D, Johnson, Aaron J
Format: Article
Language:English
Subjects:
Animal models
Animals
Antigen (tumor-associated)
Antigens
Antigens, Viral - genetics
Antigens, Viral - immunology
Biology and life sciences
Cancer vaccines
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cell Line, Tumor
Cytokines - immunology
Cytokines - metabolism
Epitopes, T-Lymphocyte - immunology
Flow Cytometry
Genetic aspects
Genetic Vectors - genetics
Genetic Vectors - immunology
Glioma
Glioma - genetics
Glioma - immunology
Gliomas
Health aspects
Humans
Immunization
Immunotherapy
Lymphocytes
Lymphocytes T
Medicine and health sciences
Melanoma
Melanoma, Experimental - genetics
Melanoma, Experimental - immunology
Mice, Inbred C57BL
Neoplasms, Experimental - genetics
Neoplasms, Experimental - immunology
Ovalbumin
Ovalbumin - genetics
Ovalbumin - immunology
Physiological aspects
Picornaviridae - genetics
Picornaviridae - immunology
Picornavirus
Prevention
T cell receptors
Theiler's encephalomyelitis virus
Theilovirus - genetics
Theilovirus - immunology
Tumor Burden - genetics
Tumor Burden - immunology
Vaccination
Vaccination - methods
Vaccines
Viruses
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Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0162064