Adenovirus based virus-like-vaccines targeting endogenous retroviruses can eliminate growing colorectal cancers in mice.

Adenovirus based virus-like-vaccines targeting endogenous retroviruses can eliminate growing colorectal cancers in mice. Oncotarget. 2019 Feb 15;10(14):1458-1472 Authors: Neukirch L, Nielsen TK, Laursen H, Daradoumis J, Thirion C, Holst PJ Abstract 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...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research