Human Ad19a/64 HERV-W Vaccines Uncover Immunosuppression Domain-Dependent T-Cell Response Differences in Inbred Mice.

Abstract

Expression of human endogenous retrovirus type W (HERV-W) has been linked to cancer, making HERV-W antigens potential targets for therapeutic cancer vaccines. In a previous study, we effectively treated established tumours in mice by using adenoviral-vectored vaccines targeting the murine endogenous retrovirus envelope and group-specific antigen (Gag) of melanoma-associated retrovirus (MelARV) in combination with anti-PD-1. To break the immunological tolerance to MelARV, we mutated the immunosuppressive domain (ISD) of the MelARV envelope. However, reports on the immunogenicity of the HERV-W envelope, Syncytin-1, and its ISD are conflicting. To identify the most effective HERV-W cancer vaccine candidate, we evaluated the immunogenicity of vaccines encoding either the wild-type or mutated HERV-W envelope ISD in vitro and in vivo. Here, we show that the wild-type HERV-W vaccine generated higher activation of murine antigen-presenting cells and higher specific T-cell responses than the ISD-mutated counterpart. We also found that the wild-type HERV-W vaccine was sufficient to increase the probability of survival in mice subjected to HERV-W envelope-expressing tumours compared to a control vaccine. These findings provide the foundation for developing a therapeutic cancer vaccine targeting HERV-W-positive cancers in humans.

• Authors: Isabella Skandorff, Emeline Ragonnaud, Jasmin Gille, Anne-Marie Andersson, Silke Schrödel, Lara Duvnjak, Louise Turner, Christian Thirion, Ralf Wagner, Peter Johannes Holst
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 24 Issue 12 (Jun 09 2023) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 37373123 (Publication Type: Journal Article)

Chemical References

• Cancer Vaccines

Topics

• Humans
• Animals
• Mice
• Endogenous Retroviruses (genetics)
• T-Lymphocytes
• Cancer Vaccines
• Neoplasms
• Immunosuppression Therapy