Viral particles support prophylactic vaccination against breast cancer

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

Jarolim Mimotop  1

Artificial structures of tumour antigens, mimotopes, applied in vaccinations of cancer patients can trigger a long-term immune response. For the vaccine, however, a carrier is required that triggers an immune response itself. 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 have already received a 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. 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 thus reducing the 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. No chemical after-treatment is necessary and the structure is retained. “After specifically selecting mimotopes with HER2-antibodies, we get a full vaccine ready to use,” said Jensen-Jarolim from the Messerli Research Institute at Vetmeduni Vienna.

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.

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

Read the press release “Viral particles support prophylactic vaccination against breast cancer” for more information.

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