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



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.



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.



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.
Center of Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria; Biomedical International R+D GmbH, Vienna, Austria.
Josef
J
Singer
Biomedical International R+D GmbH, Vienna, Austria; Comparative Medicine, Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna, and University Vienna, Vienna, Austria.
Krisztina
K
Manzano-Szalai
Center of Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria; Comparative Medicine, Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna, and University Vienna, Vienna, Austria.
Judit
J
Fazekas
Center of Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria; Biomedical International R+D GmbH, Vienna, Austria.
Kathrin
K
Thell
Center of Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna , Vienna, Austria.
Anna
A
Bentley-Lukschal
Center of Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna , Vienna, Austria.
Caroline
C
Stremnitzer
Comparative Medicine, Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna, and University Vienna , Vienna, Austria.
Franziska
F
Roth-Walter
MediGene AG , Martinsried, Germany.
Margit
M
Weghofer
MediGene AG , Martinsried, Germany.
Mirko
M
Ritter
MediGene AG , Martinsried, Germany.
Kerstin
K
Pino Tossi
MediGene AG , Martinsried, Germany.
Markus
M
Hörer
MediGene AG, Martinsried, Germany; ImevaX GmbH Munich, Germany.
Uwe
U
Michaelis
Center of Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria; Biomedical International R+D GmbH, Vienna, Austria; Comparative Medicine, Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna, and University Vienna, Vienna, Austria.
Erika
E
Jensen-Jarolim
AAV; HER-2; adeno-associated virus; cancer vaccine; mimotope