Effective Delivery of Antigen-Encapsulin Nanoparticle Fusions to Dendritic Cells Leads to Antigen-Specific Cytotoxic T Cell Activation and Tumor Rejection
- Authors
- Choi, Bongseo; Moon, Hyojin; Hong, Sung Joon; Shin, Changsik; Do, Yoonkyung; Ryu, Seongho; Kang, Sebyung
- Issue Date
- Aug-2016
- Publisher
- American Chemical Society
- Keywords
- encapsulin; antigen delivery; vaccination; dendritic cells; cytotoxic T cells
- Citation
- ACS Nano, v.10, no.8, pp 7339 - 7350
- Pages
- 12
- Journal Title
- ACS Nano
- Volume
- 10
- Number
- 8
- Start Page
- 7339
- End Page
- 7350
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/18645
- DOI
- 10.1021/acsnano.5b08084
- ISSN
- 1936-0851
1936-086X
- Abstract
- 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-gamma, a cytokine critical in tumor rejection. Here, we employed recently established protein cage nano particles, 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 naive 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-gamma 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.
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- Appears in
Collections - Graduate School > Department of Integrated Biomedical Science > 1. Journal Articles
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