| Autor: |
Ingrid Fert, Laëtitia Douguet, Benjamin Vesin, Fanny Moncoq, Amandine Noirat, Pierre Authié, Sylvain Ciret, Fabien Le Chevalier, Catherine Blanc, Yakov Vitrenko, Pierre Charneau, Laleh Majlessi, François Anna |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
npj Vaccines, Vol 9, Iss 1, Pp 1-14 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2059-0105 |
| DOI: |
10.1038/s41541-024-00894-0 |
| Popis: |
Abstract We recently developed an immuno-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 a homologous 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 chain mRNA, 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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