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Broadening the message : a nanovaccine co-loaded with messenger RNA and U+03B1-GalCer induces antitumor immunity through conventional and natural killer T cells

Tijdschriftbijdrage - Tijdschriftartikel

Ondertitel:Broadening the message : a nanovaccine co-loaded with messenger RNA and alpha-GalCer induces antitumor immunity through conventional and natural killer T cells
Messenger RNA encoding tumor antigens has the potential to evoke effective antitumor immunity. This study reports on a nanoparticle platform, named mRNA Galsomes, that successfully co-delivers nucleoside-modified antigen-encoding mRNA and the glycolipid antigen and immunopotentiator U+03B1-galactosylceramide (U+03B1-GC) to antigen-presenting cells after intravenous administration. By co-formulating low doses of U+03B1-GC, mRNA Galsomes induce a pluripotent innate and adaptive tumor-specific immune response in mice, with invariant natural killer T cells (iNKT) as a driving force. In comparison, mRNA Galsomes exhibit advantages over the state-of-the-art cancer vaccines using unmodified ovalbumin (OVA)-encoding mRNA, as we observed up to seven times more tumor-infiltrating antigen-specific cytotoxic T cells, combined with a strong iNKT cell and NK cell activation. In addition, the presence of suppressive myeloid cells (myeloid-derived suppressor cells and tumor-associated macrophages) in the tumor microenvironment was significantly lowered. Owing to these antitumor effects, OVA mRNA Galsomes significantly reduced tumor growth in established E.G7-OVA lymphoma, with a complete tumor rejection in 40% of the animals. Moreover, therapeutic vaccination with mRNA Galsomes enhanced the responsiveness to treatment with a PD-L1 checkpoint inhibitor in B16-OVA melanoma, as evidenced by a synergistic reduction of tumor outgrowth and a significantly prolonged median survival. Taken together, these data show that intravenously administered mRNA Galsomes can provide controllable, multifaceted, and effective antitumor immunity, especially when combined with checkpoint inhibition.
Tijdschrift: ACS NANO
ISSN: 1936-086X
Issue: 2
Volume: 13
Pagina's: 1655 - 1669
BOF-keylabel:ja
IOF-keylabel:ja
BOF-publication weight:10
CSS-citation score:2
Auteurs:National
Authors from:Higher Education
Toegankelijkheid:Open