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

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).


Journal Article | Published | English
Author
Singer, Josef; Manzano-Szalai, Krisztina; Singer, JuditIST Austria ; Thell, Kathrin; Bentley-Lukschal, Anna; Stremnitzer, Caroline; Roth-Walter, Franziska; Weghofer, Margit; Ritter, Mirko; Pino Tossi, Kerstin; Hörer, Markus; Michaelis, Uwe
All
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.
Publishing Year
Date Published
2016-06-30
Journal Title
OncoImmunology
Volume
5
Issue
7
Article Number
e1171446
ISSN
IST-REx-ID

Cite this

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. OncoImmunology. 2016;5(7). doi:10.1080/2162402x.2016.1171446
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. OncoImmunology, 5(7). https://doi.org/10.1080/2162402x.2016.1171446
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.” OncoImmunology 5, no. 7 (2016). https://doi.org/10.1080/2162402x.2016.1171446.
J. Singer et al., “Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform,” OncoImmunology, vol. 5, no. 7, 2016.
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).
Singer, Josef, et al. “Proof of Concept Study with an HER-2 Mimotope Anticancer Vaccine Deduced from a Novel AAV-Mimotope Library Platform.” OncoImmunology, vol. 5, no. 7, e1171446, Taylor & Francis, 2016, doi:10.1080/2162402x.2016.1171446.
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