Vaccination with TMEV Xho1-OVA8 enhances tumor antigen-restricted CD8+ T cell responses in the CNS, delays tumor progression, and extends survival in mice bearing GL261-Quad gliomas.

Two weeks post-GL261-Quad tumor introduction, mice were treated with control or recombinant picornavirus. (A,B) At five weeks, brain infiltrating lymphocytes were isolated, gated based on CD45 expression, and analyzed for CD8 and K^b:OVA_257–264 tetramer positivity. (A) Representative FACS plots and (B) mean percent of K^b:OVA_257–264+ cells per CD8+ cells demonstrate a significant increase in tumor antigen-restricted CD8+ T cells infiltrating the brain following intracranial (N = 9) or intraperitoneal (N = 10 mice) TMEV Xho1-OVA8 vaccine administration compared to TMEV-wt. Percent of K^b:OVA_257–264+ / CD8+ calculated as Q2-2/(Q2-2+Q4-2)*100. (C,E) Mean bioluminescence intensity (p/sec) of GL261-Quad glioma-bearing mice treated with TMEV-wt or recombinant TMEV Xho1-OVA8 picornavirus. Mice receiving (C) intracranial (N = 15 mice) or (E) intraperitoneal (N = 13 mice) TMEV Xho1-OVA8 treatment displayed significantly delayed progression of established gliomas compared to TMEV-wt treated controls. (D,F) Delayed tumor progression is accompanied by a significant increase in survival for mice treated with TMEV Xho1-OVA8 via (D) intracranial or (F) intraperitoneal administration. Arrow denotes time of vaccine administration. (G) RT-PCR analysis of RNA isolated from brains of glioma-bearing mice demonstrates a significant reduction in transgene expression following treatment with TMEV Xho1-OVA8 compared to TMEV-wt treated controls. Error bars indicate SEM. * denotes p<0.05, ** denotes p<0.01, ***denotes p<0.001.