دورية أكاديمية
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
| العنوان: | 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 |
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| المؤلفون: | Huang, J., Zhou, J., Ghinnagow, R., Seki, T., Iketani, S., Soulard, D., Paczkowski, P., Tsuji, Y., MacKay, S., Cruz, L.J., Trottein, F., Tsuji, M. |
| المصدر: | Frontiers in Immunology |
| سنة النشر: | 2020 |
| المجموعة: | Leiden Repository (Leiden University) |
| مصطلحات موضوعية: | nanovaccine, targeting, human CD141(+) DCs, iNKT cells, alpha-galactosylceramide, CD8(+) T cells, human immune system mice, melanoma |
| الوصف: | 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. ; Radiology |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.02043/fullTest; lumc-id: 111607110; https://hdl.handle.net/1887/3184215Test |
| DOI: | 10.3389/fimmu.2020.02043/full |
| DOI: | 10.3389/fimmu.2020.02043 |
| الإتاحة: | https://doi.org/10.3389/fimmu.2020.02043Test https://hdl.handle.net/1887/3184215Test |
| رقم الانضمام: | edsbas.C54481FA |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2020.02043/full |
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