title: Engineered Human Ferritin Nanoparticles for Direct Delivery of Tumor Antigens to Lymph Node and Cancer Immunotherapy.
abstract: Efficient delivery of tumor-specific antigens (TSAs) to lymph nodes (LNs) is essential to eliciting robust immune response for cancer immunotherapy but still remains unsolved. Herein, we evaluated the direct LN-targeting performance of four different protein nanoparticles with different size, shape, and origin [Escherichia coli DNA binding protein (DPS), Thermoplasma acidophilum proteasome (PTS), hepatitis B virus capsid (HBVC), and human ferritin heavy chain (hFTN)] in live mice, using an optical fluorescence imaging system. Based on the imaging results, hFTN that shows rapid LN targeting and prolonged retention in LNs was chosen as a carrier of the model TSA [red fluorescence protein (RFP)], and the flexible surface architecture of hFTN was engineered to densely present RFPs on the hFTN surface through genetic modification of subunit protein of hFTN. The RFP-modified hFTN rapidly targeted LNs, sufficiently exposed RFPs to LN immune cells during prolonged period of retention in LNs, induced strong RFP-specific cytotoxic CD8+T cell response, and notably inhibited RFP-expressing melanoma tumor growth in live mice. This suggests that the strategy using protein nanoparticles as both TSA-carrying scaffold and anti-cancer vaccine holds promise for clinically effective immunotherapy of cancer.
authors.affiliation: Department of Chemical and Biological Engineering, Korea University, Anam-Dong 5-1, Seongbuk-Gu, Seoul 136-713, Republic of Korea.
authors.forename: Bo-Ram
authors.initials: BR
authors.lastname: Lee
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ho Kyung
authors.initials: HK
authors.lastname: Ko
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Chemical and Biological Engineering, Korea University, Anam-Dong 5-1, Seongbuk-Gu, Seoul 136-713, Republic of Korea.
authors.forename: Keum Young
authors.initials: KY
authors.lastname: Ahn
authors.affiliation: Division of Infection and Immunology, Graduate School of Medicine, Korea University, Anam-dong 5-1, Seongbuk-gu, Seoul 136-701, Republic of Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Division of Infection and Immunology, Graduate School of Medicine, Korea University, Anam-dong 5-1, Seongbuk-gu, Seoul 136-701, Republic of Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Na
authors.affiliation: Division of Infection and Immunology, Graduate School of Medicine, Korea University, Anam-dong 5-1, Seongbuk-gu, Seoul 136-701, Republic of Korea.
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Chemical and Biological Engineering, Korea University, Anam-Dong 5-1, Seongbuk-Gu, Seoul 136-713, Republic of Korea.
authors.forename: Jeewon
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D005293:Ferritins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007167:Immunotherapy / Q000379:methods*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism*; D008545:Melanoma / Q000628:therapy; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D004337:Drug Carriers; D005293:Ferritins