Lipo-Based Vaccines as an Approach to Target Dendritic Cells for Induction of T- and iNKT Cell Responses.

Autor:	Stolk DA; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., de Haas A; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Vree J; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.; Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Duinkerken S; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Lübbers J; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., van de Ven R; Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.; Department of Otolaryngology/Head and Neck Surgery, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Ambrosini M; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Kalay H; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Bruijns S; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., van der Vliet HJ; Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.; LAVA Therapeutics, Utrecht, Netherlands., de Gruijl TD; Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., van Kooyk Y; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2020 May 27; Vol. 11, pp. 990. Date of Electronic Publication: 2020 May 27 (Print Publication: 2020).
DOI:	10.3389/fimmu.2020.00990
Abstrakt:	In this study we developed a liposome-based vaccine containing palmitoylated synthetic long peptides (SLP) and alpha galactosylceramide (αGC) to specifically target dendritic cells (DC) for activation of both innate (invariant natural killer T-cells [iNKT]) and adaptive (CD8 + T-cells) players of the immune system. Combination of model tumor specific antigens (gp100/MART-1) formulated as a SLP and αGC in one liposome results in strong activation of CD8 + and iNKT, as measured by IFNγ secretion. Moreover, addition of lipo-Lewis Y (Le Y ) to the liposomes for C-type lectin targeting increased not only uptake by monocyte-derived dendritic cells (moDC), dermal dendritic cells and Langerhans cells but also enhanced gp100-specific CD8 + T- and iNKT cell activation by human skin-emigrated antigen presenting cells in an ex vivo explant model. Loading of moDC with liposomes containing Le Y also showed priming of MART-1 26-35L specific CD8 + T-cells. In conclusion, chemically linking a lipid tail to a glycan-based targeting moiety and SLP combined with αGC in one liposome allows for easy generation of vaccine formulations that target multiple skin DC subsets and induce tumor antigen specific CD8 + T- and iNKT cells. These liposomes present a new vaccination strategy against tumors. (Copyright © 2020 Stolk, de Haas, Vree, Duinkerken, Lübbers, van de Ven, Ambrosini, Kalay, Bruijns, van der Vliet, de Gruijl and van Kooyk.)
Databáze:	MEDLINE
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