iNKT/CD1d-antitumor immunotherapy significantly increases the efficacy of therapeutic CpG/peptide-based cancer vaccine.

Détails

Ressource 1Télécharger: BIB_4C145C87702F.P001.pdf (1721.17 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_4C145C87702F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
iNKT/CD1d-antitumor immunotherapy significantly increases the efficacy of therapeutic CpG/peptide-based cancer vaccine.
Périodique
Journal for Immunotherapy of Cancer
Auteur(s)
Corgnac S., Perret R., Zhang L., Mach J.P., Romero P., Donda A.
ISSN
2051-1426 (Electronic)
ISSN-L
2051-1426
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
2
Numéro
1
Pages
39
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
BACKGROUND: Therapeutic cancer vaccines aim to boost the natural immunity against transformed cancer cells, and a series of adjuvants and co-stimulatory molecules have been proposed to enhance the immune response against weak self-antigens expressed on cancer cells. For instance, a peptide/CpG-based cancer vaccine has been evaluated in several clinical trials and was shown in pre-clinical studies to favor the expansion of effector T versus Tregs cells, resulting in a potent antitumor activity, as compared to other TLR ligands. Alternatively, the adjuvant activity of CD1d-restricted invariant NKT cells (iNKT) on the innate and adaptive immunity is well demonstrated, and several CD1d glycolipid ligands are under pre-clinical and clinical evaluation. Importantly, additive or even synergistic effects have been shown upon combined CD1d/NKT agonists and TLR ligands. The aim of the present study is to combine the activation and tumor targeting of activated iNKT, NK and T cells.
METHODS: Activation and tumor targeting of iNKT cells via recombinant α-galactosylceramide (αGC)-loaded CD1d-anti-HER2 fusion protein (CD1d-antitumor) is combined or not with OVA peptide/CpG vaccine. Circulating and intratumoral NK and H-2Kb/OVA-specific CD8 responses are monitored, as well as the state of activation of dendritic cells (DC) with regard to activation markers and IL-12 secretion. The resulting antitumor therapy is tested against established tumor grafts of B16 melanoma cells expressing human HER2 and ovalbumin.
RESULTS: The combined CD1d/iNKT antitumor therapy and CpG/peptide-based immunization leads to optimized expansion of NK and OVA-specific CD8 T cells (CTLs), likely resulting from the maturation of highly pro-inflammatory DCs as seen by a synergistic increase in serum IL-12. The enhanced innate and adaptive immune responses result in higher tumor inhibition that correlates with increased numbers of OVA-specific CTLs at the tumor site. Antibody-mediated depletion experiments further demonstrate that in this context, CTLs rather than NK cells are essential for the enhanced tumor inhibition.
CONCLUSIONS: Altogether, our study in mice demonstrates that αGC/CD1d-antitumor fusion protein greatly increases the efficacy of a therapeutic CpG-based cancer vaccine, first as an adjuvant during T cell priming and second, as a therapeutic agent to redirect immune responses to the tumor site.
Pubmed
Open Access
Oui
Création de la notice
16/01/2015 13:46
Dernière modification de la notice
20/08/2019 14:00
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