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

Frontiers in Immunology

Tanja D. de Gruijl¹  Jana Vree¹  Dorian A. Stolk²  Hakan Kalay²  Joyce Lübbers²  Yvette van Kooyk²  Sven Bruijns²  Aram de Haas²  Sanne Duinkerken²  Martino Ambrosini²  Rieneke van de Ven³  Hans J. van der Vliet⁴ 

[1] Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, Amsterdam, Netherlands;Department of Molecular Cell Biology and Immunology, 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;LAVA Therapeutics, Utrecht, Netherlands;

关键词: dendritic cell;    DC-SIGN;    langerin;    liposome;    targeting;    iNKT;   

DOI  :  10.3389/fimmu.2020.00990

来源: DOAJ

【 摘 要 】

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 (LeY) 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 LeY also showed priming of MART-126−35L 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.

【 授权许可】

Unknown