Bivalent therapeutic vaccine against HPV16/18 genotypes consisting of a fusion protein between the extra domain A from human fibronectin and HPV16/18 E7 viral antigens.

Détails

ID Serval
serval:BIB_8F1E679B0434
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Bivalent therapeutic vaccine against HPV16/18 genotypes consisting of a fusion protein between the extra domain A from human fibronectin and HPV16/18 E7 viral antigens.
Périodique
Journal for immunotherapy of cancer
Auteur(s)
Arribillaga L., Echeverria I., Belsue V., Gomez T., Lozano T., Casares N., Villanueva L., Domingos-Pereira S., Romero P.J., Nardelli-Haefliger D., Hervás-Stubbs S., Sarobe P., Rodriguez M.J., Carrascosa J.L., Zürcher T., Lasarte J.J.
ISSN
2051-1426 (Electronic)
ISSN-L
2051-1426
Statut éditorial
Publié
Date de publication
06/2020
Peer-reviewed
Oui
Volume
8
Numéro
1
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
In vivo targeting of human papillomavirus (HPV) derived antigens to dendritic cells might constitute an efficient immunotherapeutic strategy against cervical cancer. In previous works, we have shown that the extra domain A from murine fibronectin (mEDA) can be used to target antigens to toll-like receptor 4 (TLR4) expressing dendritic cells and induce strong antigen-specific immune responses. In the present study, we have produced a bivalent therapeutic vaccine candidate consisting of the human EDA (hEDA) fused to E7 proteins from HPV16 and HPV18 (hEDA-HPVE7-16/18) and evaluate its potential as a therapeutic vaccine against cervical cancer.
Recombinant fusion proteins containing HPV E7 proteins from HPV16 and HPV18 virus subtypes fused to hEDA were produced and tested in vitro on their capacity to bind TLR4 and induce the production of tumor necrosis factor-α or interleukin (IL)-12 by human monocytes and dendritic cells. The immunogenicity and potential therapeutic activity of the vaccine in combination with cisplatin or with the TLR3 agonist molecules polyinosinic-polycytidylic acid (Poly IC) or Poly ICLC was evaluated in mice bearing subcutaneous or genital orthotopic HPV16 TC-1 tumors.
hEDA-HPVE7-16/18 prototype vaccine binds human TLR4 and stimulate TLR4-dependent signaling pathways and IL-12 production by human monocyte-derived dendritic cell. Vaccination with hEDA-HPVE7-16/18 induced strong HPVE7-specific Cytotoxic T lymphocyte (CTL) responses and eliminated established tumors in the TC-1-based tumor model. The antitumor efficacy was significantly improved by combining the fusion protein with cisplatin or with the TLR-3 ligand Poly IC and especially with the stabilized analog Poly ICLC. Moreover, hEDA-HPVE7-16/18+Poly ICLC induced full tumor regression in 100% of mice bearing orthotopic genital HPV tumors.
Our results suggest that this therapeutic vaccine formulation may be an effective treatment for cervical tumors that do not respond to current therapies.
Mots-clé
T-lymphocytes, dendritic cells, genital neoplasms, female, immunotherapy, vaccination
Pubmed
Open Access
Oui
Création de la notice
03/07/2020 17:31
Dernière modification de la notice
05/09/2020 5:26
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