Full eradication of pre‐clinical human papilloma virus‐induced tumors by a lentiviral vaccine

Autor: Laëtitia Douguet, Ingrid Fert, Jodie Lopez, Benjamin Vesin, Fabien Le Chevalier, Fanny Moncoq, Pierre Authié, Trang‐My Nguyen, Amandine Noirat, Fabien Névo, Catherine Blanc, Maryline Bourgine, David Hardy, François Anna, Laleh Majlessi, Pierre Charneau
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 15, Iss 10, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 1757-4684
1757-4676
DOI: 10.15252/emmm.202317723
Popis: Abstract Human papillomavirus (HPV) infections are the cause of all cervical and numerous oropharyngeal and anogenital cancers. The currently available HPV vaccines, which induce neutralizing antibodies, have no therapeutic effect on established tumors. Here, we developed an immuno‐oncotherapy against HPV‐induced tumors based on a non‐integrative lentiviral vector encoding detoxified forms of the Early E6 and E7 oncoproteins of HPV16 and 18 genotypes, namely, “Lenti‐HPV‐07”. A single intramuscular injection of Lenti‐HPV‐07 into mice bearing established HPV‐induced tumors resulted in complete tumor eradication in 100% of the animals and was also effective against lung metastases. This effect correlated with CD8+ T‐cell induction and profound remodeling of the tumor microenvironment. In the intra‐tumoral infiltrates of vaccinated mice, the presence of large amounts of activated effector, resident memory, and transcription factor T cell factor‐1 (TCF‐1)+ “stem‐like” CD8+ T cells was associated with full tumor eradication. The Lenti‐HPV‐07‐induced immunity was long‐lasting and prevented tumor growth after a late re‐challenge, mimicking tumor relapse. Lenti‐HPV‐07 therapy synergizes with an anti‐checkpoint inhibitory treatment and therefore shows promise as an immuno‐oncotherapy against established HPV‐mediated malignancies.
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