Effective treatment of established GL261 murine gliomas through picornavirus vaccination-enhanced tumor antigen-specific CD8+ T cell responses

Danielle N. Renner, Fang Jin, Adam J. Litterman, Alexis J. Balgeman, Lisa M. Hanson, Jeffrey D. Gamez, Michael Chae, Brett L. Carlson, Jann N Sarkaria, Ian F Parney, John R. Ohlfest, Istvan Pirko, Kevin D. Pavelko, Aaron J. Johnson

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Glioblastoma (GBM) is among the most invasive and lethal of cancers, frequently infiltrating surrounding healthy tissue and giving rise to rapid recurrence. It is therefore critical to establish experimental model systems and develop therapeutic approaches that enhance antitumor immunity. In the current study, we have employed a newly developed murine glioma model to assess the efficacy of a novel picornavirus vaccination approach for the treatment of established tumors. The GL261-Quad system is a variation of the GL261 syngeneic glioma that has been engineered to expresses model T cell epitopes including OVA<inf>257-264</inf>. MRI revealed that both GL261 and GL261-Quad tumors display characteristic features of human gliomas such as heterogeneous gadolinium leakage and larger T2 weighted volumes. Analysis of brain-infiltrating immune cells demonstrated that GL261-Quad gliomas generate detectable CD8+ T cell responses toward the tumor-specific K<sup>b</sup>:OVA<inf>257-264</inf> antigen. Enhancing this response via a single intracranial or peripheral vaccination with picornavirus expressing the OVA<inf>257-264</inf> antigen increased anti-tumor CD8+ T cells infiltrating the brain, attenuated progression of established tumors, and extended survival of treated mice. Importantly, the efficacy of the picornavirus vaccination is dependent on functional cytotoxic activity of CD8+ T cells, as the beneficial response was completely abrogated in mice lacking perforin expression. Therefore, we have developed a novel system for evaluating mechanisms of anti-tumor immunity in vivo, incorporating the GL261-Quad model, 3D volumetric MRI, and picornavirus vaccination to enhance tumor-specific cytotoxic CD8+ T cell responses and track their effectiveness at eradicating established gliomas in vivo.

Original languageEnglish (US)
Article numbere0125565
JournalPLoS One
Volume10
Issue number5
DOIs
StatePublished - May 1 2015

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Picornaviridae
T-cells
Neoplasm Antigens
Glioma
Tumors
Vaccination
T-lymphocytes
vaccination
antigens
T-Lymphocytes
neoplasms
mice
Neoplasms
Magnetic resonance imaging
Therapeutics
Brain
Immunity
immunity
Antigens
Perforin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Effective treatment of established GL261 murine gliomas through picornavirus vaccination-enhanced tumor antigen-specific CD8+ T cell responses. / Renner, Danielle N.; Jin, Fang; Litterman, Adam J.; Balgeman, Alexis J.; Hanson, Lisa M.; Gamez, Jeffrey D.; Chae, Michael; Carlson, Brett L.; Sarkaria, Jann N; Parney, Ian F; Ohlfest, John R.; Pirko, Istvan; Pavelko, Kevin D.; Johnson, Aaron J.

In: PLoS One, Vol. 10, No. 5, e0125565, 01.05.2015.

Research output: Contribution to journalArticle

Renner, DN, Jin, F, Litterman, AJ, Balgeman, AJ, Hanson, LM, Gamez, JD, Chae, M, Carlson, BL, Sarkaria, JN, Parney, IF, Ohlfest, JR, Pirko, I, Pavelko, KD & Johnson, AJ 2015, 'Effective treatment of established GL261 murine gliomas through picornavirus vaccination-enhanced tumor antigen-specific CD8+ T cell responses', PLoS One, vol. 10, no. 5, e0125565. https://doi.org/10.1371/journal.pone.0125565
Renner, Danielle N. ; Jin, Fang ; Litterman, Adam J. ; Balgeman, Alexis J. ; Hanson, Lisa M. ; Gamez, Jeffrey D. ; Chae, Michael ; Carlson, Brett L. ; Sarkaria, Jann N ; Parney, Ian F ; Ohlfest, John R. ; Pirko, Istvan ; Pavelko, Kevin D. ; Johnson, Aaron J. / Effective treatment of established GL261 murine gliomas through picornavirus vaccination-enhanced tumor antigen-specific CD8+ T cell responses. In: PLoS One. 2015 ; Vol. 10, No. 5.
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AU - Carlson, Brett L.

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AU - Parney, Ian F

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AU - Pirko, Istvan

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