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Article Dans Une Revue NPJ vaccines Année : 2024

T-cell immunity induced and reshaped by an anti-HPV immuno-oncotherapeutic lentiviral vector

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Werecently developed animmuno-oncotherapy against human papillomavirus (HPV)-induced tumors based on a lentiviral vector encoding the Early E6 and E7 oncoproteins of HPV16 and HPV18 genotypes, namely “Lenti-HPV-07”. The robust and long-lasting anti-tumor efficacy of Lenti-HPV-07 is dependent on CD8+ T-cell induction and remodeling of the tumor microenvironment. Here, we first established that anti-vector immunity induced by Lenti-HPV-07 prime has no impact on the efficacy of ahomologous boost to amplify anti-HPV T-cell immunity. To longitudinally monitor the evolution of the T-cell repertoire generated after the prime, homologous or heterologous boost with Lenti-HPV-07, we tracked T-cell clonotypes by deep sequencing of T-Cell Receptor (TCR) variable β and α chainmRNA, applied to whole peripheral blood cells (PBL) and a T cell population specific of an immunodominant E7HPV16 epitope. We observed a hyper-expansion of clonotypes post prime, accompanied by increased frequencies of HPV-07-specific T cells. Additionally, there was a notable diversification of clonotypes post boost in whole PBL, but not in the E7HPV16-specific T cells. We then demonstrated that the effector functions of such Lenti-HPV-07-induced T cells synergize with anti-checkpoint inhibitory treatments by systemic administration of anti-TIM3 or anti-NKG2A monoclonal antibodies. While Lenti-HPV-07 is about to enter a Phase I/IIa clinical trial, these results will help better elucidate its mode of action in immunotherapy against established HPV-mediated malignancies.
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pasteur-04627281 , version 1 (27-06-2024)

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Ingrid Fert, Laëtitia Douguet, Benjamin Vesin, Fanny Moncoq, Amandine Noirat, et al.. T-cell immunity induced and reshaped by an anti-HPV immuno-oncotherapeutic lentiviral vector. NPJ vaccines, 2024, 9 (1), pp.102. ⟨10.1038/s41541-024-00894-0⟩. ⟨pasteur-04627281⟩
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