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Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform
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 gene...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006910/ https://www.ncbi.nlm.nih.gov/pubmed/27622022 http://dx.doi.org/10.1080/2162402X.2016.1171446 |
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author | Singer, Josef Manzano-Szalai, Krisztina Fazekas, Judit Thell, Kathrin Bentley-Lukschal, Anna Stremnitzer, Caroline Roth-Walter, Franziska Weghofer, Margit Ritter, Mirko Pino Tossi, Kerstin Hörer, Markus Michaelis, Uwe Jensen-Jarolim, Erika |
author_facet | Singer, Josef Manzano-Szalai, Krisztina Fazekas, Judit Thell, Kathrin Bentley-Lukschal, Anna Stremnitzer, Caroline Roth-Walter, Franziska Weghofer, Margit Ritter, Mirko Pino Tossi, Kerstin Hörer, Markus Michaelis, Uwe Jensen-Jarolim, Erika |
author_sort | Singer, Josef |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5006910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-50069102016-09-12 Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform Singer, Josef Manzano-Szalai, Krisztina Fazekas, Judit Thell, Kathrin Bentley-Lukschal, Anna Stremnitzer, Caroline Roth-Walter, Franziska Weghofer, Margit Ritter, Mirko Pino Tossi, Kerstin Hörer, Markus Michaelis, Uwe Jensen-Jarolim, Erika Oncoimmunology Original Research 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. Taylor & Francis 2016-04-21 /pmc/articles/PMC5006910/ /pubmed/27622022 http://dx.doi.org/10.1080/2162402X.2016.1171446 Text en © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. |
spellingShingle | Original Research Singer, Josef Manzano-Szalai, Krisztina Fazekas, Judit Thell, Kathrin Bentley-Lukschal, Anna Stremnitzer, Caroline Roth-Walter, Franziska Weghofer, Margit Ritter, Mirko Pino Tossi, Kerstin Hörer, Markus Michaelis, Uwe Jensen-Jarolim, Erika Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform |
title | Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform |
title_full | Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform |
title_fullStr | Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform |
title_full_unstemmed | Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform |
title_short | Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform |
title_sort | proof of concept study with an her-2 mimotope anticancer vaccine deduced from a novel aav-mimotope library platform |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006910/ https://www.ncbi.nlm.nih.gov/pubmed/27622022 http://dx.doi.org/10.1080/2162402X.2016.1171446 |
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