Effective Delivery of Antigen-Encapsulin Nanoparticle Fusions to Dendritic Cells Leads to Antigen-Specific Cytotoxic T Cell Activation and Tumor Rejection
| Autor: | Yoonkyung Do, Hyojin Moon, Seongho Ryu, Bongseo Choi, Sung Joon Hong, Sebyung Kang, Changsik Shin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Ovalbumin T cell medicine.medical_treatment Antigen presentation General Physics and Astronomy 02 engineering and technology Biology CD8-Positive T-Lymphocytes Lymphocyte Activation 03 medical and health sciences Mice Immune system Antigen Cancer immunotherapy medicine Cytotoxic T cell Animals General Materials Science Antigen-presenting cell Drug Carriers General Engineering Dendritic Cells 021001 nanoscience & nanotechnology Molecular biology Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Nanoparticles 0210 nano-technology CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | ACS nano. 10(8) |
| ISSN: | 1936-086X |
| Popis: | In cancer immunotherapy, robust and efficient activation of cytotoxic CD8(+) T cell immune responses is a promising, but challenging task. Dendritic cells (DCs) are well-known professional antigen presenting cells that initiate and regulate antigen-specific cytotoxic CD8(+) T cells that kill their target cells directly as well as secrete IFN-γ, a cytokine critical in tumor rejection. Here, we employed recently established protein cage nanoparticles, encapsulin (Encap), as antigenic peptide nanocarriers by genetically incorporating the OT-1 peptide of ovalbumin (OVA) protein to the three different positions of the Encap subunit. With them, we evaluated their efficacy in activating DC-mediated antigen-specific T cell cytotoxicity and consequent melanoma tumor rejection in vivo. DCs efficiently engulfed Encap and its variants (OT-1-Encaps), which carry antigenic peptides at different positions, and properly processed them within phagosomes. Delivered OT-1 peptides were effectively presented by DCs to naïve CD8(+) T cells successfully, resulting in the proliferation of antigen-specific cytotoxic CD8(+) T cells. OT-1-Encap vaccinations in B16-OVA melanoma tumor bearing mice effectively activated OT-1 peptide specific cytotoxic CD8(+) T cells before or even after tumor generation, resulting in significant suppression of tumor growth in prophylactic as well as therapeutic treatments. A large number of cytotoxic CD8(+) T cells that actively produce both intracellular and secretory IFN-γ were observed in tumor-infiltrating lymphocytes collected from B16-OVA tumor masses originally vaccinated with OT-1-Encap-C upon tumor challenges. The approaches we describe herein may provide opportunities to develop epitope-dependent vaccination systems that stimulate and/or modulate efficient and epitope-specific cytotoxic T cell immune responses in nonpathogenic diseases. |
| Databáze: | OpenAIRE |
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