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  • Open Access

Radiation therapy and vaccination against tumor-specific EGFRvIII effectively clears tumors in a murine model of head and neck squamous cell carcinoma

  • 1, 2,
  • 1,
  • 1,
  • 3,
  • 1, 4, 5,
  • 1, 4, 6 and
  • 1, 4
Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P78

https://doi.org/10.1186/2051-1426-3-S2-P78

  • Published:

Keywords

  • Squamous Cell Carcinoma
  • Deletional Mutant
  • Tumor Regression
  • Listeria
  • Listeria Monocytogenes

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.

Authors’ Affiliations

(1)
Earle A. Chiles Research Institute, Portland, OR, USA
(2)
Molecular Microbiology and Immunology, OHSU, Portland, OR, USA
(3)
Aduro Biotech, Berkeley, CA, USA
(4)
Providence Cancer Center, The Oregon Clinic, Portland, OR, USA
(5)
The Oregon Clinic, Portland, OR, USA
(6)
Robert W. Franz Cancer Research Center, Portland, OR, USA

Copyright

© Uhde et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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