Skandorff, Isabella and Ragonnaud, Emeline and Gille, Jasmin and Andersson, Anne-Marie and Schroedel, Silke and Duvnjak, Lara and Turner, Louise and Thirion, Christian and Wagner, Ralf and Holst, Peter Johannes (2023) Human Ad19a/64 HERV-W Vaccines Uncover Immunosuppression Domain-Dependent T-Cell Response Differences in Inbred Mice. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (12): 9972. ISSN 1661-6596, 1422-0067
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENVELOPE PROTEIN; ENDOGENOUS RETROVIRUSES; NEURAL-NETWORKS; EXPRESSION; PEPTIDE; SYNCYTIN; SEQUENCE; PROLIFERATION; FUSION; FAMILY; adenovirus vector; human endogenous retrovirus type W (HERV-W); immunosuppressive domain; Syncytin-1 |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2024 09:34 |
| Last Modified: | 23 Mar 2024 09:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60408 |
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