Adenovirus based virus-like-vaccines targeting endogenous retroviruses can eliminate growing colorectal cancers in
Lasse Neukirch1,2, Tea Kirkegaard Nielsen1, Henriette Laursen1
1University of Copenhagen, Center for Medical Parasitology, The Panum Institute, DK2200 Copenhagen, Denmark.
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 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.
Insights
A novel vaccine targeting endogenous retroviruses (ERVs) shows promise in cancer therapy. This strategy effectively uses T cell responses to inhibit tumor growth and progression, offering a new tool against diverse ERV-bearing cancers.
Area of Science:
- Oncology
- Immunology
- Virology
Background:
- Endogenous retroviruses (ERVs) constitute 8% of the human genome and are implicated in cancer development and progression.
- The murine melanoma-associated retrovirus (MelARV) model provides a system to investigate ERV-targeted cancer therapies.
Purpose of the Study:
- To design and evaluate a novel vaccine strategy (Ad5-MelARV) for targeting ERV-expressing tumors.
- To assess the vaccine's ability to induce humoral and cellular immune responses against ERV-associated cancers.
Main Methods:
- Adenovirus-based vaccine (Ad5-MelARV) encoding MelARV Gag and Env proteins was developed.
- Vaccine administered to BALB/c mice to assess T cell responses and anti-tumor efficacy against CT26 colorectal and 4T1 breast cancer cell lines.
- Combination therapy with anti-PD-1 checkpoint inhibitor was evaluated.
Main Results:
- A single Ad5-MelARV vaccination induced robust T cell responses, preventing CT26 tumor growth and progression.
- The vaccine, even without antibody induction, demonstrated significant anti-tumor effects.
- Combination with anti-PD-1 resulted in complete tumor regression.
- Immune responses were effective against both CT26 and 4T1 cancer cell lines, indicating broad applicability.
Conclusions:
- The Ad5-MelARV vaccine strategy successfully elicits T cell-mediated anti-tumor immunity against ERV-expressing cancers.
- This approach holds potential as a novel therapeutic tool for various ERV-bearing tumors.
- Combination therapy with checkpoint inhibitors can enhance vaccine efficacy.
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