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Targeted Co-delivery of Tumor Antigen and α-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 α-galactosylceramide (α-GalCer), a potent agonist for invariant Natural Killer T (iNKT) cells, to cross-priming CD8α+ 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 CD8α+ DCs - and deliver both tumor Ag (Melan A) and α-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.
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https://www.hal.inserm.fr/inserm-02960071
Contributor : François Trottein <>
Submitted on : Wednesday, October 7, 2020 - 12:56:40 PM
Last modification on : Monday, April 26, 2021 - 3:10:02 PM
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Jing Huang, Jing Zhou, Reem Ghinnagow, Toshiyuki Seki, Sho Iketani, et al.. Targeted Co-delivery of Tumor Antigen and α-Galactosylceramide to CD141+ Dendritic Cells Induces a Potent Tumor Antigen-Specific Human CD8+ T Cell Response in Human Immune System Mice. Frontiers in Immunology, Frontiers, 2020, 11, pp.2043. ⟨10.3389/fimmu.2020.02043⟩. ⟨inserm-02960071⟩

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