{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:09:05Z","timestamp":1792800545444,"version":"4.5.0"},"reference-count":74,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"InProTher ApS","award":["9065-00055B"],"award-info":[{"award-number":["9065-00055B"]}]},{"name":"Sirion Biotech GmbH","award":["9065-00055B"],"award-info":[{"award-number":["9065-00055B"]}]},{"name":"Innovation Fund Denmark","award":["9065-00055B"],"award-info":[{"award-number":["9065-00055B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Endogenous retroviruses (ERVs) account for 8% of our genome, and, although they are usually silent in healthy tissues, they become reactivated and expressed in pathological conditions such as cancer. Several studies support a functional role of ERVs in tumour development and progression, specifically through their envelope (Env) protein, which contains a region described as an immunosuppressive domain (ISD). We have previously shown that targeting of the murine ERV (MelARV) Env using virus-like vaccine (VLV) technology, consisting of an adenoviral vector encoding virus-like particles (VLPs), induces protection against small tumours in mice. Here, we investigate the potency and efficacy of a novel MelARV VLV with a mutated ISD (ISDmut) that can modify the properties of the adenoviral vaccine-encoded Env protein. We show that the modification of the vaccine\u2019s ISD significantly enhanced T-cell immunogenicity in both prime and prime-boost vaccination regimens. The modified VLV in combination with an \u03b1-PD1 checkpoint inhibitor (CPI) exhibited excellent curative efficacy against large established colorectal CT26 tumours in mice. Furthermore, only ISDmut-vaccinated mice that survived CT26 challenge were additionally protected against rechallenge with a triple-negative breast cancer cell line (4T1), showing that our modified VLV provides cross-protection against different tumour types expressing ERV-derived antigens. We envision that translating these findings and technology into human ERVs (HERVs) could provide new treatment opportunities for cancer patients with unmet medical needs.<\/jats:p>","DOI":"10.3390\/v15040926","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T08:41:52Z","timestamp":1680770512000},"page":"926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["An Endogenous Retrovirus Vaccine Encoding an Envelope with a Mutated Immunosuppressive Domain in Combination with Anti-PD1 Treatment Eradicates Established Tumours in Mice"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7438-3222","authenticated-orcid":false,"given":"Joana","family":"Daradoumis","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark"},{"name":"InProTher, Bioinnovation Institute, COBIS, Ole Maal\u00f8es Vej 3, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5460-7789","authenticated-orcid":false,"given":"Emeline","family":"Ragonnaud","sequence":"additional","affiliation":[{"name":"InProTher, Bioinnovation Institute, COBIS, Ole Maal\u00f8es Vej 3, 2200 Copenhagen, Denmark"},{"name":"Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4380-0521","authenticated-orcid":false,"given":"Isabella","family":"Skandorff","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark"},{"name":"InProTher, Bioinnovation Institute, COBIS, Ole Maal\u00f8es Vej 3, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9897-3972","authenticated-orcid":false,"given":"Karen N\u00f8rgaard","family":"Nielsen","sequence":"additional","affiliation":[{"name":"InProTher, Bioinnovation Institute, COBIS, Ole Maal\u00f8es Vej 3, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1966-2912","authenticated-orcid":false,"given":"Amaia Vergara","family":"Bermejo","sequence":"additional","affiliation":[{"name":"InProTher, Bioinnovation Institute, COBIS, Ole Maal\u00f8es Vej 3, 2200 Copenhagen, Denmark"},{"name":"Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Andersson","sequence":"additional","affiliation":[{"name":"InProTher, Bioinnovation Institute, COBIS, Ole Maal\u00f8es Vej 3, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1520-8299","authenticated-orcid":false,"given":"Silke","family":"Schroedel","sequence":"additional","affiliation":[{"name":"Sirion Biotech GmbH, 82166 Graefelfing, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Thirion","sequence":"additional","affiliation":[{"name":"Sirion Biotech GmbH, 82166 Graefelfing, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2055-4743","authenticated-orcid":false,"given":"Lasse","family":"Neukirch","sequence":"additional","affiliation":[{"name":"InProTher, Bioinnovation Institute, COBIS, Ole Maal\u00f8es Vej 3, 2200 Copenhagen, Denmark"},{"name":"Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Johannes","family":"Holst","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark"},{"name":"InProTher, Bioinnovation Institute, COBIS, Ole Maal\u00f8es Vej 3, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. 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