Carboplatin/paclitaxel, E7-vaccination and intravaginal CpG as tri-therapy towards efficient regression of genital HPV16 tumors.

Détails

Ressource 1Télécharger: 31060612_BIB_7B25C5D053CD.pdf (1109.66 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_7B25C5D053CD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Carboplatin/paclitaxel, E7-vaccination and intravaginal CpG as tri-therapy towards efficient regression of genital HPV16 tumors.
Périodique
Journal for immunotherapy of cancer
Auteur(s)
Domingos-Pereira S., Galliverti G., Hanahan D., Nardelli-Haefliger D.
ISSN
2051-1426 (Electronic)
ISSN-L
2051-1426
Statut éditorial
Publié
Date de publication
06/05/2019
Peer-reviewed
Oui
Volume
7
Numéro
1
Pages
122
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
High-risk human papillomavirus (HPV) are responsible for genital and oral cancers associated with the expression of the E6/E7 HPV oncogenes. Therapeutic vaccines targeting those oncogenes can only partially control tumor progression, highlighting the necessity to investigate different treatment strategies. Using the genital orthotopic HPV16 TC-1 model, herein we sequentially investigated in progressively more stringent settings the effects of systemic administration of carboplatin/paclitaxel (C + P) chemotherapy combined with HPV16-E7 synthetic long peptide (E7LP) vaccination, followed by intravaginal immunostimulation with the synthetic toll-like-receptor-9 agonist CpG. Our data show that systemic delivery of C + P prior to E7LP vaccination significantly increased mice survival. This survival benefit was associated with both reduced genital tumor growth at the time of vaccination, and a decreased infiltration of Ly6G myeloid cells and tumor-associated macrophages. Adding intravaginal CpG, which results in increased E7-specific CD8 T cells locally, to E7LP vaccination and the chemotherapy formed a tri-therapy, which significantly increased mice survival as compared to any of the dual treatments. When the tri-therapy was further refined by using a recently optimized nanoparticle-conjugated E7LP vaccine, even larger end-stage genital-TC-1 tumors responded, with 90% of mice showing a survival benefit as compared to 30% of mice with the tri-therapy involving the traditional E7LP 'liquid' vaccine. C + P is commonly used to treat cervical cancer patients and its combination with E7/E6 vaccination is currently being tested in a phase I/II trial (NCT02128126). Our data suggests that new vaccine formulations combined with local immunostimulation and standard-of-care chemotherapy have promise to further benefit patients with HPV-associated cancer.
Mots-clé
Carboplatin/paclitaxel, E7 long peptide and nanoparticle vaccination, HPV genital cancer, Intravaginal CpG immunostimulation
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/05/2019 17:37
Dernière modification de la notice
30/04/2021 7:12
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