{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","day":"30","publisher":"Taylor & Francis","date_created":"2020-08-10T11:54:03Z","volume":5,"abstract":[{"lang":"eng","text":"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."}],"_id":"8241","oa":1,"publication_status":"published","publication":"OncoImmunology","language":[{"iso":"eng"}],"quality_controlled":"1","title":"Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform","main_file_link":[{"url":"https://doi.org/10.1080/2162402X.2016.1171446","open_access":"1"}],"intvolume":"         5","date_published":"2016-06-30T00:00:00Z","extern":"1","citation":{"apa":"Singer, J., Manzano-Szalai, K., Singer, J., Thell, K., Bentley-Lukschal, A., Stremnitzer, C., … Jensen-Jarolim, E. (2016). Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform. <i>OncoImmunology</i>. Taylor &#38; Francis. <a href=\"https://doi.org/10.1080/2162402x.2016.1171446\">https://doi.org/10.1080/2162402x.2016.1171446</a>","ista":"Singer J, Manzano-Szalai K, Singer J, Thell K, Bentley-Lukschal A, Stremnitzer C, Roth-Walter F, Weghofer M, Ritter M, Pino Tossi K, Hörer M, Michaelis U, Jensen-Jarolim E. 2016. Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform. OncoImmunology. 5(7), e1171446.","chicago":"Singer, Josef, Krisztina Manzano-Szalai, Judit Singer, Kathrin Thell, Anna Bentley-Lukschal, Caroline Stremnitzer, Franziska Roth-Walter, et al. “Proof of Concept Study with an HER-2 Mimotope Anticancer Vaccine Deduced from a Novel AAV-Mimotope Library Platform.” <i>OncoImmunology</i>. Taylor &#38; Francis, 2016. <a href=\"https://doi.org/10.1080/2162402x.2016.1171446\">https://doi.org/10.1080/2162402x.2016.1171446</a>.","ieee":"J. Singer <i>et al.</i>, “Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform,” <i>OncoImmunology</i>, vol. 5, no. 7. Taylor &#38; Francis, 2016.","ama":"Singer J, Manzano-Szalai K, Singer J, et al. Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform. <i>OncoImmunology</i>. 2016;5(7). doi:<a href=\"https://doi.org/10.1080/2162402x.2016.1171446\">10.1080/2162402x.2016.1171446</a>","mla":"Singer, Josef, et al. “Proof of Concept Study with an HER-2 Mimotope Anticancer Vaccine Deduced from a Novel AAV-Mimotope Library Platform.” <i>OncoImmunology</i>, vol. 5, no. 7, e1171446, Taylor &#38; Francis, 2016, doi:<a href=\"https://doi.org/10.1080/2162402x.2016.1171446\">10.1080/2162402x.2016.1171446</a>.","short":"J. Singer, K. Manzano-Szalai, J. Singer, K. Thell, A. Bentley-Lukschal, C. Stremnitzer, F. Roth-Walter, M. Weghofer, M. Ritter, K. Pino Tossi, M. Hörer, U. Michaelis, E. Jensen-Jarolim, OncoImmunology 5 (2016)."},"month":"06","year":"2016","publication_identifier":{"issn":["2162-402X"]},"status":"public","author":[{"full_name":"Singer, Josef","last_name":"Singer","first_name":"Josef"},{"first_name":"Krisztina","last_name":"Manzano-Szalai","full_name":"Manzano-Szalai, Krisztina"},{"id":"36432834-F248-11E8-B48F-1D18A9856A87","full_name":"Fazekas, Judit","last_name":"Fazekas","orcid":"0000-0002-8777-3502","first_name":"Judit"},{"first_name":"Kathrin","last_name":"Thell","full_name":"Thell, Kathrin"},{"full_name":"Bentley-Lukschal, Anna","first_name":"Anna","last_name":"Bentley-Lukschal"},{"first_name":"Caroline","last_name":"Stremnitzer","full_name":"Stremnitzer, Caroline"},{"last_name":"Roth-Walter","first_name":"Franziska","full_name":"Roth-Walter, Franziska"},{"full_name":"Weghofer, Margit","last_name":"Weghofer","first_name":"Margit"},{"full_name":"Ritter, Mirko","first_name":"Mirko","last_name":"Ritter"},{"first_name":"Kerstin","last_name":"Pino Tossi","full_name":"Pino Tossi, Kerstin"},{"full_name":"Hörer, Markus","last_name":"Hörer","first_name":"Markus"},{"full_name":"Michaelis, Uwe","first_name":"Uwe","last_name":"Michaelis"},{"first_name":"Erika","last_name":"Jensen-Jarolim","full_name":"Jensen-Jarolim, Erika"}],"oa_version":"Published Version","date_updated":"2021-01-12T08:17:41Z","doi":"10.1080/2162402x.2016.1171446","type":"journal_article","article_type":"original","issue":"7","article_number":"e1171446"}