Adenovirus based virus-like-vaccines targeting endogenous retroviruses can eliminate growing colorectal cancers in mice
| Autor: | Peter Johannes Holst, Henriette Laursen, Christian Thirion, Lasse Neukirch, Tea Kirkegaard Nielsen, Joana Daradoumis |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
T cell Endogenous retrovirus virus-like particles Virus endogenous retroviruses 03 medical and health sciences 0302 clinical medicine Retrovirus Immune system medicine cancer biology Melanoma Cancer virus-like-vaccines biology.organism_classification medicine.disease adenoviral vectors Vaccination 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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