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Targeted co-delivery of tumor antigen and alpha-galactosylceramide to CD141(+) dendritic cells induces a potent tumor antigen-specific human CD8(+) T cell response in human immune system mice
- Source :
- Frontiers in Immunology, 11. FRONTIERS MEDIA SA, Frontiers in Immunology, Frontiers in Immunology, 2020, 11, pp.2043. ⟨10.3389/fimmu.2020.02043⟩, Frontiers in Immunology, Frontiers, 2020, 11, pp.2043. ⟨10.3389/fimmu.2020.02043⟩, Frontiers in Immunology, Vol 11 (2020)
- Publication Year :
- 2020
-
Abstract
- Active co-delivery of tumor antigens (Ag) and alpha-galactosylceramide (alpha-GalCer), a potent agonist for invariant Natural Killer T (iNKT) cells, to cross-priming CD8 alpha(+) 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 alpha(+) DCs - and deliver both tumor Ag (Melan A) and alpha-GalCer. This nanovaccine was inoculated into humanized mice that mimic the human immune system (HIS) and possess functionaliNKT 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 andiNKT 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 humaniNKT cells to license cross-priming DCsin vivoand adds a new dimension to the current strategy of cancer vaccine development.
- Subjects :
- 0301 basic medicine
Proteomics
Thrombomodulin
Epitopes, T-Lymphocyte
CD8-Positive T-Lymphocytes
Mice
0302 clinical medicine
Mice, Inbred NOD
T-Lymphocyte Subsets
Cytotoxic T cell
Immunology and Allergy
alpha-galactosylceramide
human immune system mice
Original Research
α-galactosylceramide
CD8(+) T cells
Chemistry
Melanoma
ELISPOT
Tumor antigen
3. Good health
[SDV.IMM]Life Sciences [q-bio]/Immunology
nanovaccine
Single-Cell Analysis
lcsh:Immunologic diseases. Allergy
human CD141+ DCs
[SDV.IMM] Life Sciences [q-bio]/Immunology
Immunology
Galactosylceramides
Mice, Transgenic
chemical and pharmacologic phenomena
CD8+ T cells
Cancer Vaccines
human CD141(+) DCs
Immunophenotyping
03 medical and health sciences
Immune system
Antigen
Antigens, Neoplasm
medicine
melanoma
Animals
Humans
Lectins, C-Type
targeting
iNKT cells
Dendritic Cells
medicine.disease
030104 developmental biology
Receptors, Mitogen
Cancer research
Cancer vaccine
lcsh:RC581-607
CD8
Biomarkers
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology, 11. FRONTIERS MEDIA SA, Frontiers in Immunology, Frontiers in Immunology, 2020, 11, pp.2043. ⟨10.3389/fimmu.2020.02043⟩, Frontiers in Immunology, Frontiers, 2020, 11, pp.2043. ⟨10.3389/fimmu.2020.02043⟩, Frontiers in Immunology, Vol 11 (2020)
- Accession number :
- edsair.doi.dedup.....da61d6a3cbe282ae349622d7862a40ce