PMID- 27390910 OWN - NLM STAT- MEDLINE DCOM- 20180727 LR - 20181202 IS - 1936-086X (Electronic) IS - 1936-0851 (Linking) VI - 10 IP - 8 DP - 2016 Aug 23 TI - Effective Delivery of Antigen-Encapsulin Nanoparticle Fusions to Dendritic Cells Leads to Antigen-Specific Cytotoxic T Cell Activation and Tumor Rejection. PG - 7339-50 LID - 10.1021/acsnano.5b08084 [doi] AB - 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 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 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. FAU - Choi, Bongseo AU - Choi B AD - Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , Ulsan, 689-798, Korea. FAU - Moon, Hyojin AU - Moon H AD - Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , Ulsan, 689-798, Korea. FAU - Hong, Sung Joon AU - Hong SJ AD - Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , Ulsan, 689-798, Korea. FAU - Shin, Changsik AU - Shin C AD - Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , Ulsan, 689-798, Korea. FAU - Do, Yoonkyung AU - Do Y AD - Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , Ulsan, 689-798, Korea. FAU - Ryu, Seongho AU - Ryu S AD - Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University , Cheonan, 336-745, Korea. FAU - Kang, Sebyung AU - Kang S AD - Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , Ulsan, 689-798, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160713 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 RN - 0 (Drug Carriers) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Animals MH - CD8-Positive T-Lymphocytes MH - *Dendritic Cells MH - *Drug Carriers MH - *Lymphocyte Activation MH - Mice MH - Mice, Inbred C57BL MH - *Nanoparticles MH - Ovalbumin MH - *T-Lymphocytes, Cytotoxic OTO - NOTNLM OT - antigen delivery OT - cytotoxic T cells OT - dendritic cells OT - encapsulin OT - vaccination EDAT- 2016/07/09 06:00 MHDA- 2018/07/28 06:00 CRDT- 2016/07/09 06:00 PHST- 2016/07/09 06:00 [entrez] PHST- 2016/07/09 06:00 [pubmed] PHST- 2018/07/28 06:00 [medline] AID - 10.1021/acsnano.5b08084 [doi] PST - ppublish SO - ACS Nano. 2016 Aug 23;10(8):7339-50. doi: 10.1021/acsnano.5b08084. Epub 2016 Jul 13.