Adenovirus based virus-like-vaccines targeting endogenous retroviruses can eliminate growing colorectal cancers in mice
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Lasse Neukirch1,2, Tea Kirkegaard Nielsen1, Henriette Laursen1, Joana Daradoumis1,4, Christian Thirion3 and Peter Johannes Holst1,4
1University of Copenhagen, Center for Medical Parasitology, The Panum Institute, DK2200 Copenhagen, Denmark
2Clinical Cooperation Unit Applied Tumor Immunity, National Center for Tumor Diseases and German Cancer Research Center, 69120 Heidelberg, Germany
3Sirion Biotech GmbH, 82152 Planegg-Martinsried, Germany
4InProTher ApS, DK2200 Copenhagen, Denmark
Peter Johannes Holst, email: [email protected]
Keywords: adenoviral vectors, cancer, endogenous retroviruses, virus-like particles, virus-like-vaccines
Received: June 26, 2018 Accepted: February 01, 2019 Published: February 15, 2019
Endogenous retroviruses (ERVs) that make up 8% of the human genome have been associated with the development and progression of cancer. The murine model system of the melanoma associated retrovirus (MelARV), which is expressed in different murine cancer cell lines, can be used to study mechanisms and therapeutic approaches against ERVs in cancer. We designed a vaccine strategy (Ad5-MelARV) of adenoviruses encoding the MelARV proteins Gag and Env that assemble in vivo into virus-like particles displaying the cancer-associated MelARV Env to the immune system. The novel vaccine was designed to induce both humoral as well as cellular immune responses in order to attack ERV expressing tumor cells. Despite a lack of antibody induction, we found that T cell responses were strong enough to prevent colorectal CT26 tumor growth and progression in BALB/c mice after a single vaccination before or after tumor challenge. A combination with the checkpoint inhibitor anti-PD-1 further increased the efficacy of the vaccination leading to complete tumor regression. Furthermore, immune responses in vaccinated mice were not restricted to only one cancer cell line but vaccinated animals were also protected from a rechallenge with the distinct breast cancer cell line 4T1. Thus, the developed vaccine strategy could represent a novel tool to successfully target diverse ERV-bearing tumors in cancer patients.
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