@article{8241,
  abstract     = {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.},
  author       = {Singer, Josef and Manzano-Szalai, Krisztina and Fazekas, Judit and Thell, Kathrin and Bentley-Lukschal, Anna and Stremnitzer, Caroline and Roth-Walter, Franziska and Weghofer, Margit and Ritter, Mirko and Pino Tossi, Kerstin and Hörer, Markus and Michaelis, Uwe and Jensen-Jarolim, Erika},
  issn         = {2162-402X},
  journal      = {OncoImmunology},
  number       = {7},
  publisher    = {Taylor & Francis},
  title        = {{Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform}},
  doi          = {10.1080/2162402x.2016.1171446},
  volume       = {5},
  year         = {2016},
}