title: Effective Delivery of Antigen-Encapsulin Nanoparticle Fusions to Dendritic Cells Leads to Antigen-Specific Cytotoxic T Cell Activation and Tumor Rejection.
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-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.
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , Ulsan, 689-798, Korea.
authors.forename: Bongseo
authors.initials: B
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , Ulsan, 689-798, Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Moon
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , Ulsan, 689-798, Korea.
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Hong
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , Ulsan, 689-798, Korea.
authors.forename: Changsik
authors.initials: C
authors.lastname: Shin
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , Ulsan, 689-798, Korea.
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Do
authors.affiliation: Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University , Cheonan, 336-745, Korea.
authors.forename: Seongho
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , Ulsan, 689-798, Korea.
authors.forename: Sebyung
authors.initials: S
authors.lastname: Kang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes; D003713:Dendritic Cells; D004337:Drug Carriers; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D010047:Ovalbumin; D013602:T-Lymphocytes, Cytotoxic
chemical_list: D004337:Drug Carriers; D010047:Ovalbumin
keywords: antigen delivery; cytotoxic T cells; dendritic cells; encapsulin; vaccination