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Article Dans Une Revue EMBO Molecular Medicine Année : 2023

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

Ingrid Fert
Benjamin Vesin
Fanny Moncoq
Pierre Authié
Amandine Noirat
Pierre Charneau

Résumé

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 anticheckpoint inhibitory treatment and therefore shows promise as an immuno-oncotherapy against established HPV-mediated malignancies.
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pasteur-04225883 , version 1 (03-10-2023)

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Laëtitia Douguet, Ingrid Fert, Jodie Lopez, Benjamin Vesin, Fabien Le Chevalier, et al.. Full eradication of pre-clinical human papilloma virus-induced tumors by a lentiviral vaccine. EMBO Molecular Medicine, In press, pp.e17723. ⟨10.15252/emmm.202317723⟩. ⟨pasteur-04225883⟩

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