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Targeted Co-delivery of Tumor Antigen and ?-Galactosylceramide to CD141+ Dendritic Cells Induces a Potent Tumor Antigen-Specific Human CD8+ T Cell Response in Human Immune System Mice.


ABSTRACT: Active co-delivery of tumor antigens (Ag) and ?-galactosylceramide (?-GalCer), a potent agonist for invariant Natural Killer T (iNKT) cells, to cross-priming CD8?+ dendritic cells (DCs) was previously shown to promote strong anti-tumor responses in mice. Here, we designed a nanoparticle-based vaccine able to target human CD141+ (BDCA3+) DCs - the equivalent of murine CD8?+ DCs - and deliver both tumor Ag (Melan A) and ?-GalCer. This nanovaccine was inoculated into humanized mice that mimic the human immune system (HIS) and possess functional iNKT cells and CD8+ T cells, called HIS-CD8/NKT mice. We found that multiple immunizations of HIS-CD8/NKT mice with the nanovaccine resulted in the activation and/or expansion of human CD141+ DCs and iNKT cells and ultimately elicited a potent Melan-A-specific CD8+ T cell response, as determined by tetramer staining and ELISpot assay. Single-cell proteomics further detailed the highly polyfunctional CD8+ T cells induced by the nanovaccine and revealed their predictive potential for vaccine potency. This finding demonstrates for the first time the unique ability of human iNKT cells to license cross-priming DCs in vivo and adds a new dimension to the current strategy of cancer vaccine development.

SUBMITTER: Huang J 

PROVIDER: S-EPMC7461784 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Targeted Co-delivery of Tumor Antigen and α-Galactosylceramide to CD141<sup>+</sup> Dendritic Cells Induces a Potent Tumor Antigen-Specific Human CD8<sup>+</sup> T Cell Response in Human Immune System Mice.

Huang Jing J   Zhou Jing J   Ghinnagow Reem R   Seki Toshiyuki T   Iketani Sho S   Soulard Daphnée D   Paczkowski Patrick P   Tsuji Yukiko Y   MacKay Sean S   Cruz Luis Javier LJ   Trottein François F   Tsuji Moriya M  

Frontiers in immunology 20200818


Active co-delivery of tumor antigens (Ag) and α-galactosylceramide (α-GalCer), a potent agonist for invariant Natural Killer T (<i>i</i>NKT) cells, to cross-priming CD8α<sup>+</sup> dendritic cells (DCs) was previously shown to promote strong anti-tumor responses in mice. Here, we designed a nanoparticle-based vaccine able to target human CD141<sup>+</sup> (BDCA3<sup>+</sup>) DCs - the equivalent of murine CD8α<sup>+</sup> DCs - and deliver both tumor Ag (Melan A) and α-GalCer. This nanovaccine  ...[more]

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