Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform

Josef Singer, Krisztina Manzano-Szalai, Judit Fazekas, Kathrin Thell, Anna Bentley-Lukschal, Caroline Stremnitzer, Franziska Roth-Walter, Margit Weghofer, Mirko Ritter, Kerstin Pino Tossi, Markus Hörer, Uwe Michaelis, Erika Jensen-Jarolim*

*Corresponding author for this work

Research output: Journal article (peer-reviewed)Journal article

17 Citations (Scopus)


Background: Anticancer vaccines could represent a valuable complementary strategy to established therapies, especially in settings of early stage and minimal residual disease. HER-2 is an important target for immunotherapy and addressed by the monoclonal antibody trastuzumab. We have previously generated HER-2 mimotope peptides from phage display libraries. The synthesized peptides were coupled to carriers and applied for epitope-specific induction of trastuzumab-like IgG. For simplification and to avoid methodological limitations of synthesis and coupling chemistry, we herewith present a novel and optimized approach by using adeno-associated viruses (AAV) as effective and high-density mimotope-display system, which can be directly used for vaccination. Methods: An AAV capsid display library was constructed by genetically incorporating random peptides in a plasmid encoding the wild-type AAV2 capsid protein. AAV clones, expressing peptides specifically reactive to trastuzumab, were employed to immunize BALB/c mice. Antibody titers against human HER-2 were determined, and the isotype composition and functional properties of these were tested. Finally, prophylactically immunized mice were challenged with human HER-2 transfected mouse D2F2/E2 cells. Results: HER-2 mimotope AAV-vaccines induced antibodies specific to human HER-2. Two clones were selected for immunization of mice, which were subsequently grafted D2F2/E2 cells. Both mimotope AAV clones delayed the growth of tumors significantly, as compared to controls. Conclusion: In this study, a novel mimotope AAV-based platform was created allowing the isolation of mimotopes, which can be directly used as anticancer vaccines. The example of trastuzumab AAV-mimotopes demonstrates that this vaccine strategy could help to establish active immunotherapy for breast-cancer patients.

Original languageEnglish
Article numbere1171446
Issue number7
Publication statusPublished - 02 Jul 2016
Externally publishedYes


  • AAV
  • adeno-associated virus
  • cancer vaccine
  • HER-2
  • mimotope

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology


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