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Targeted Delivery of α-Galactosylceramide to CD8α + Dendritic Cells Optimizes Type I NKT Cell–Based Antitumor Responses

Abstract : Immunotherapy aiming at enhancing innate and acquired host immunity is a promising approach for cancer treatment. The invariant NKT (iNKT) cell ligand α-galactosylceramide (α-GalCer) holds great promise in cancer therapy, although several concerns limit its use in clinics, including the uncontrolled response it promotes when delivered in a nonvectorized form. Therefore, development of delivery systems to in vivo target immune cells might be a valuable option to optimize iNKT cell-based antitumor responses. Using dendritic cell (DC)-depleted mice, DC transfer experiments, and in vivo active cell targeting, we show that presentation of α-GalCer by DCs not only triggers optimal primary iNKT cell stimulation, but also maintains secondary iNKT cell activation after challenge. Furthermore, targeted delivery of α-GalCer to CD8α(+) DCs, by means of anti-DEC205 decorated nanoparticles, enhances iNKT cell-based transactivation of NK cells, DCs, and γδ T cells. We report that codelivery of α-GalCer and protein Ag to CD8α(+) DCs triggers optimal Ag-specific Ab and cytotoxic CD8(+) T cell responses. Finally, we show that targeting nanoparticles containing α-GalCer and Ag to CD8α(+) DCs promotes potent antitumor responses, both in prophylactic and in therapeutic settings. Our data may have important implications in tumor immunotherapy and vaccine development.
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Contributor : François Trottein Connect in order to contact the contributor
Submitted on : Sunday, January 12, 2020 - 11:25:25 AM
Last modification on : Monday, December 13, 2021 - 1:54:02 PM

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Elodie Macho-Fernandez, Luis Javier Cruz, Reem Ghinnagow, Josette Fontaine, Emilie Bialecki, et al.. Targeted Delivery of α-Galactosylceramide to CD8α + Dendritic Cells Optimizes Type I NKT Cell–Based Antitumor Responses. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2014, 193 (2), pp.961-969. ⟨10.4049/jimmunol.1303029⟩. ⟨inserm-02436034⟩



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