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  • Poster presentation
  • Open Access

Epitope-optimization creates highly immunogenic alpha fetoprotein antigen to break immune tolerance and potently activates CD8 T cells to prevents autochthonous hepatocellular carcinoma

  • 1,
  • 1,
  • 3,
  • 1,
  • 2,
  • 1,
  • 1,
  • 3 and
  • 1
Journal for ImmunoTherapy of Cancer20131 (Suppl 1) :P216

https://doi.org/10.1186/2051-1426-1-S1-P216

  • Published:

Keywords

  • Tumor Cell
  • Hepatocellular Carcinoma
  • Good Chance
  • Vaccinia
  • Immune Tolerance

In this study, we investigated whether mouse alpha fetoprotein (mAFP), the shared self/tumor antigen of hepatocellular carcinoma (HCC), could be rationally engineered to create effective vaccine to break tolerance and potently activate CD8 T cells to prevent clinically-relevant carcinogen-induced autochthonous HCC. We found that the computer-guided epitope-optimization created optimized opt-mAFP and that immunization with lentivector (lv) expressing opt-mAFP, but not wt-mAFP, potently activated CD8 cells specific for three novel H-2b restricted CD8 epitopes, which cross-recognized wt-mAFP epitopes naturally processed and presented by wt-mAFP+ tumor cells. Immunization with opt-mAFP-lv, but not wt-mAFP-lv, completely protected mice from wt-mAFP+ tumor challenge and effectively prevented carcinogen-induced autochthonous HCC. Prime-boost with opt-mAFP-lv and vaccinia vector opt-mAFP-vv significantly increased the wt-mAFP-specific CD8 T cells that were highly responsive to emerging HCC tumor cells in the liver, enhancing prevention of autochthonous HCC. Our data demonstrate that epitope-optimization creates immunogenic opt-mAFP that is able to break tolerance and activate potent CD8 responses, which can cross-recognize wt-mAFP peptides, but also recognize and kill mAFP+ tumor cells. Our study provides a practical roadmap to develop effective human vaccines that should have a better chance of success than the current human HCC vaccines based on native wt-AFP.

Authors’ Affiliations

(1)
Cancer Center, Georgia Regents University, Augusta, GA, USA
(2)
Surgery, Loyola University, Chicago, IL, USA
(3)
Surgery, University of Pittsburgh, Pittsburgh, PA, USA

Copyright

© Hong et al; licensee BioMed Central Ltd. 2013

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/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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