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11.10.2016 11:59

Viral particles support prophylactic vaccination against breast cancer

Mag.rer.nat Georg Mair Öffentlichkeitsarbeit und Kommunikation
Veterinärmedizinische Universität Wien

    Mimotopes applied in vaccinations of cancer patients can trigger long-term immune response. For a vaccine, however, an immune-reactive carrier is required. Researchers from the Messerli Research Institute at Vetmeduni Vienna thus produced mimotopes for HER2, a tumour antigen of about 30 percent of breast tumours, at virus-like particles of harmless adeno-associated viruses (AAV) without chemical after-treatment and used them directly as a specific vaccine. This vaccine could serve as a prophylaxis for high-risk patients or breast cancer patients that after therapy. Treatment of canine breast tumours likewise seems possible. The results were published in OncoImmunology and Oncology Letters.

    The immune system reacts to exogenous proteins of bacteria and viruses, so-called antigens, by producing antibodies. Also characteristics of tumour cells such as a protein which is too abundant in the cell envelope are called antigens. But as they are endogenous substances, the immune system tolerates them. Targeted vaccinations can end this tolerance and trigger an immune response against the tumour cells. Artificial imitations of the surface structure of specific tumour proteins – mimotopes – are particularly suitable for immunotherapies. They stimulate the immune system to produce antibodies against the tumour antigens, too.

    Particles from Adeno associated viruses improve the production of vaccines

    Mimotopes are selected for each type of cancer from a broad range of different structure imitations – a so-called library. “If we use antibodies against tumour antigens, we can exactly select the right mimotope from the library,” explained Erika Jensen-Jarolim, principal investigator of the study from the Messerli Research Institute at Vetmeduni Vienna. However, the selected imitations alone are not a full vaccine. They have to be additionally bonded to a carrier that triggers an immune response itself as an adjuvant.
    Mimotopes have been chemically bonded to a carrier so far. But this proved disadvantageous because the structure of the mimotope can change retrospectively, leading to reduced effectiveness of the vaccine. Therefore, Jensen-Jarolim and her team used parts of adenoviruses, so-called adeno-associated viral particles (AAV particles) as carriers. These particles do not cause a disease but a strong immune response. Mimotope libraries can be developed together with the particles. Thus, no chemical after-treatment is necessary and the structure is retained. “After specifically selecting mimotopes with antibodies, we get a full vaccine ready to use,” said Jensen-Jarolim.

    Mimotope against antigen of breast cancer successfully tested

    Together with a partner from the industry, the research team successfully tested a vaccine from a new AAV mimotope library for a tumour antigen of breast cancer, the growth factor HER2. Being a signal protein in the cell membrane of tumour cells, HER2 stimulates malign growth and survival. In 30 percent of human breast tumours, this growth factor is much more abundant in the membrane than in healthy cells.
    The effectiveness of the vaccine was proved in animal tests. Mice vaccinated with the mimotope were significantly protected against growing tumours with the HER2 tumour antigen. The control group without the vaccination developed breast tumours.

    Mimotope as a prophylactic vaccination against breast cancer

    Unlike active immunotherapy with mimotopes, a passive immunotherapy with specific anti-tumour antigens has been clinically used for quite some time. In this therapy, the immune system does not react – it remains passive. Therefore, antibodies have to be administered repeatedly. The vaccination with mimotopes, however, induces long-term immune protection through the production of endogenous antibodies against HER2.
    “For this reason, a vaccination with mimotopes might also serve as a prophylaxis for high-risk patients,” said Jensen-Jarolim. “Similar to other vaccinations, the immune system remembers the administered structures. When a protein is more abundant on the cell surface of tumour cells, the immune system has already been sensitised and will react.” Such a vaccination could protect high-risk patients prophylactically and provide further protection of breast cancer patients who already received a therapy.

    Prospective vaccination also suitable for dogs

    This method does not only work for humans. The HER2 mimotopes produced for humans are also suitable for dogs. Jensen-Jarolim and her team found out in a test that 90 percent of the structures of the relevant growth factor in dogs correspond. The growth factor plays a similar role in human and canine breast cancer. “The HER2 mimotopes we found, together with the Adeno-associated viruses as a substance carrier, could be applied in human and veterinary medicine. Both medical fields could benefit from the tests,” explained Jensen-Jarolim.

    This research is the result of a public-private partnership with Biomedical International R+D GmbH, Vienna, Austria, and MediGene, Martinsried, Germany.

    The article “Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV mimotope library platform“ by Josef Singer, Krisztina Manzano-Szalai, Judit Fazekas, Kathrin Thell, Anna Bentley-Lukschal, Caroline Stremnitzer, Franziska Roth-Walter, Margit Weghofer, Mirko Ritter, Kerstin Pino Tossi, Markus Hörer, Uwe Michaelis and Erika Jensen-Jarolim was published in OncoImmunology.

    The article “Why man's best friend, the dog, could also benefit from an anti‑HER-2 vaccine (Review)“ by Judit Fazekas, Irene Fürdös, Josef Singer and Erika Jensen-Jarolim was published in Oncology Letters.

    About Messerli Research Institute
    The Messerli Research Institute was founded in 2010 with support from the Messerli Foundation (Sörenberg, Switzerland) under the management of the University of Veterinary Medicine, Vienna in cooperation with the Medical University of Vienna and the University of Vienna. The research is devoted to the interaction between humans and animals, as well as its theoretical principles in animal cognition and behavior, comparative medicine and ethics. Its work is characterized by its broad interdisciplinary approach (biology, human medicine, veterinary medicine, philosophy, psychology, law) and strong international focus.

    About the University of Veterinary Medicine, Vienna
    The University of Veterinary Medicine, Vienna in Austria is one of the leading academic and research institutions in the field of Veterinary Sciences in Europe. About 1,300 employees and 2,300 students work on the campus in the north of Vienna which also houses five university clinics and various research sites. Outside of Vienna the university operates Teaching and Research Farms.

    Scientific Contact:
    Prof. Erika Jensen-Jarolim, MD
    Messerli Research Institute, Comparative Medicine
    University of Veterinary Medicine Vienna (Vetmeduni Vienna)
    Medical University Vienna (Meduni Wien)
    University of Vienna
    T +43 664 832 6818

    Released by:
    Georg Mair
    Science Communication / Corporate Communications
    University of Veterinary Medicine Vienna (Vetmeduni Vienna)
    T +43 1 25077-1165

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    Erika Jenson-Jarolim, Josef Singer and Judit Fazekas showed that mimotopes of the tumor antigen HER2 complexed with viral-like particles can directly be used for prophylactic vaccination.

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