IMMU-72. TARGETING GLIOBLASTOMA STEM CELLS USING A SECOND-GENERATION EGFRvIII SPECIFIC PEPTIDE VACCINE STRATEGY. (5th November 2018)

• Record Type: Journal Article
• Authors: Fidanza, Mario; Gupta, Puja; Pahlke, Svenja; Wong, Albert
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi138
• Page End: vi138
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.575
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: A large proportion of GBM tumors express an altered, constitutively active version of the EGF receptor referred to as EGFRvIII. Along with increasing proliferation and inhibiting apoptosis, expression of EGFRvIII is also a GBM stem cell marker. Targeting tumor stem cells based on EGFRvIII expression may therefore improve survival for GBM patients. As such, several clinical trials using a peptide vaccine directed against EGFRvIII have shown promising results. We have explored improved versions of our original EGFRvIII peptide vaccine and have identified a candidate that shows a 60% improvement in murine subcutaneous tumor models. In this study, we further assessed the efficacy of this 2nd generation vaccine in a murine GL261 intracranial tumor model. Mice that received the EGFRvIII peptide vaccine survived 40% longer (median) than non-vaccinated mice. This response required both CD4+ and CD8+ T cells as the observed survival benefit was lost when either of these cell populations was depleted. The specificity of this vaccine strategy was valicated by an in vitro cytotoxicity assay which demonstrated that T cells derived from EGFRvIII peptide vaccinated mice were capable of specifically killing EGFRvIII expressing GL261 target cells in vitro, while demonstrating no cytotoxitiy against EGFRvIII negative cells. Treatment with the peptide vaccine increased the abundance of tumor infiltrating CD8+ T cells (p=0.0017) and altered the intra-tumoral CD4+ to CD8+ cell ratio (p=0.0015). Moreover, relative to control mice, tumor infiltrating CD8+ T cells in vaccinated mice show significant expression of the conventional immune checkpoint receptor PD-1, indicating that combinational therapies may potentiate the vaccine induced survival benefit in this model. We are currently assessing the utility of both adjuvant and immunomodulatory combinations in an attempt to further increase the efficacy of this second generation peptide vaccine.