{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:09:04Z","timestamp":1792800544302,"version":"4.5.0"},"reference-count":47,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"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":"InProTher ApS","award":["2040-00038B"],"award-info":[{"award-number":["2040-00038B"]}]},{"name":"InProTher ApS","award":["E!12151"],"award-info":[{"award-number":["E!12151"]}]},{"name":"Sirion Biotech GmbH","award":["9065-00055B"],"award-info":[{"award-number":["9065-00055B"]}]},{"name":"Sirion Biotech GmbH","award":["2040-00038B"],"award-info":[{"award-number":["2040-00038B"]}]},{"name":"Sirion Biotech GmbH","award":["E!12151"],"award-info":[{"award-number":["E!12151"]}]},{"name":"Loma Therapeutics","award":["9065-00055B"],"award-info":[{"award-number":["9065-00055B"]}]},{"name":"Loma Therapeutics","award":["2040-00038B"],"award-info":[{"award-number":["2040-00038B"]}]},{"name":"Loma Therapeutics","award":["E!12151"],"award-info":[{"award-number":["E!12151"]}]},{"DOI":"10.13039\/100012774","name":"Innovation Fund Denmark","doi-asserted-by":"publisher","award":["9065-00055B"],"award-info":[{"award-number":["9065-00055B"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012774","name":"Innovation Fund Denmark","doi-asserted-by":"publisher","award":["2040-00038B"],"award-info":[{"award-number":["2040-00038B"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012774","name":"Innovation Fund Denmark","doi-asserted-by":"publisher","award":["E!12151"],"award-info":[{"award-number":["E!12151"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union Horizon 2020","award":["9065-00055B"],"award-info":[{"award-number":["9065-00055B"]}]},{"name":"European Union Horizon 2020","award":["2040-00038B"],"award-info":[{"award-number":["2040-00038B"]}]},{"name":"European Union Horizon 2020","award":["E!12151"],"award-info":[{"award-number":["E!12151"]}]},{"name":"Federal Ministry of Education and Research","award":["9065-00055B"],"award-info":[{"award-number":["9065-00055B"]}]},{"name":"Federal Ministry of Education and Research","award":["2040-00038B"],"award-info":[{"award-number":["2040-00038B"]}]},{"name":"Federal Ministry of Education and Research","award":["E!12151"],"award-info":[{"award-number":["E!12151"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Persistent human papillomavirus (HPV) infection is responsible for practically all cervical and a high proportion of anogenital and oropharyngeal cancers. Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T-cell response; however, far from all patients elicit a sufficient immunological response. This demonstrates a translational gap between animal models and human patients. Here, we investigated the potential of a new assay consisting of co-culturing vaccine-transduced dendritic cells (DCs) with syngeneic, healthy, human peripheral blood mononuclear cells (PBMCs) to mimic a human in vivo immunization. This new promising human ex vivo PBMC assay was evaluated using an innovative therapeutic adenovirus (Adv)-based HPV vaccine encoding the E1, E2, E6, and E7 HPV16 genes. This new method allowed us to show that vaccine-transduced DCs yielded functional effector T cells and unveiled information on immunohierarchy, showing E1-specific T-cell immunodominance over time. We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors and preferably in patient samples.<\/jats:p>","DOI":"10.3390\/cancers15245863","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T11:26:52Z","timestamp":1702639612000},"page":"5863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Preferential Expansion of HPV16 E1-Specific T Cells from Healthy Donors\u2019 PBMCs after Ex Vivo Immunization with an E1E2E6E7 Fusion Antigen"],"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":"InProTher ApS, Bioinnovation Institute, Ole Maal\u00f8es Vej 3, 2200 Copenhagen, Denmark"},{"name":"Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1435-1229","authenticated-orcid":false,"given":"Mikkel Dons","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"InProTher ApS, Bioinnovation Institute, Ole Maal\u00f8es Vej 3, 2200 Copenhagen, Denmark"},{"name":"Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6066-4034","authenticated-orcid":false,"given":"Patrick","family":"Neckermann","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology & Hygiene, Molecular Microbiology (Virology), University of Regensburg, Universit\u00e4tsstra\u00dfe 31, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1056-8591","authenticated-orcid":false,"given":"Benedikt","family":"Asbach","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology & Hygiene, Molecular Microbiology (Virology), University of Regensburg, Universit\u00e4tsstra\u00dfe 31, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1520-8299","authenticated-orcid":false,"given":"Silke","family":"Schr\u00f6del","sequence":"additional","affiliation":[{"name":"Sirion Biotech GmbH, 82166 Gr\u00e4felfing, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1605-8998","authenticated-orcid":false,"given":"Christian","family":"Thirion","sequence":"additional","affiliation":[{"name":"Sirion Biotech GmbH, 82166 Gr\u00e4felfing, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology & Hygiene, Molecular Microbiology (Virology), University of Regensburg, Universit\u00e4tsstra\u00dfe 31, 93053 Regensburg, Germany"},{"name":"Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"thor Straten","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark"},{"name":"Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital, 2730 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Johannes","family":"Holst","sequence":"additional","affiliation":[{"name":"InProTher ApS, Bioinnovation Institute, Ole Maal\u00f8es Vej 3, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0675-3655","authenticated-orcid":false,"given":"Ditte","family":"Boilesen","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark"},{"name":"Loma Therapeutics ApS, Bioinnovation Institute, Ole Maal\u00f8es Vej 3, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F","article-title":"Human papillomavirus is a necessary cause of invasive cervical cancer worldwide","volume":"189","author":"Walboomers","year":"1999","journal-title":"J. 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