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Radiation therapy and vaccination against tumor-specific EGFRvIII effectively clears tumors in a murine model of head and neck squamous cell carcinoma
  1. Lauren Uhde1,2,
  2. Shelly Bambina1,
  3. Alejandro Alice1,
  4. Peter Lauer3,
  5. Marka Crittenden1,4,5,
  6. Keith S Bahjat1,4,6 and
  7. Michael Gough1,4
  1. Aff1 grid.415286.c0000 0004 0463 5556Earle A. Chiles Research Institute Portland OR USA
  2. Aff2 grid.5288.70000000097585690Molecular Microbiology and ImmunologyOHSU Portland OR USA
  3. Aff3 grid.417411.6Aduro Biotech Berkeley CA USA
  4. Aff4 grid.420050.30000 0004 0455 9389Providence Cancer CenterThe Oregon Clinic Portland OR USA
  5. Aff5 grid.420050.30000 0004 0455 9389The Oregon Clinic Portland OR USA
  6. Aff6 Robert W. Franz Cancer Research Center Portland OR USA

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Meeting abstracts

EGFRvIII is a constitutively active and tumor-specific deletional mutant of EGFR found in multiple tumor types including glioblastoma multiforme, and has been reported in head and neck squamous cell carcinomas (HNSCC). The deletion of EGFR exons 2-7 results in a novel glycine at the junction and yields a tumor-specific antigen with demonstrated immunogenicity in mice and humans. Using a live-attenuated Listeria monocytogenes- based vaccine expressing a 21-AA neo-peptide from EGFRvIII (LmEGFRvIII), we demonstrated that prophylactic vaccination protects against subsequent challenge with an EGFRvIII-expressing squamous cell carcinoma (SCCVII-EGFRvIII). Similarly, therapeutic vaccination three days post-implantation prevented outgrowth of EGFRvIII-expressing tumors but not parental EGFRvIII-negative tumors. Conversely, we found that LmEGFRvIII vaccination was insufficient to clear large established SCCVII-EGFRvIII tumors despite eliciting large numbers of polyfunctional EGFRvIII-specific CD8+ T cells. We hypothesized that localized inflammation elicited by radiation therapy could recruit EGFRvIII-specific CD8+ T cells into the tumor. We demonstrated that while neither LmEGFRvIII vaccination nor radiation therapy alone were able to control the EGFRvIII-expressing tumors, the combination of LmEGFRvIII and radiation therapy led to tumor regression and durable cures. We are currently exploring the potential mechanisms for their synergy including the role of T cell recruitment, survival and epitope spreading.