title: In vivo stepwise immunomodulation using chitosan nanoparticles as a platform nanotechnology for cancer immunotherapy.
abstract: Dentritic cell (DC)-based cancer immunotherapy faces challenges in both efficacy and practicality. However, DC-based vaccination requires multiple injections and elaborates ex vivo manipulation, which substantially limits their use. Therefore, we sought to develop a chitosan nanoparticle (CH-NP)-based platform for the next generation of vaccines to bypass the ex vivo manipulation and induce immune responses via active delivery of polyinosinic-polycytidylic acid sodium salt (poly I:C) to target Toll-like receptor 3 (TLR3) in endosomes. We developed CH-NPs encapsulating ovalbumin (OVA) as a model antigen and poly I:C as the adjuvant in an ionic complex. These CH-NPs showed increased in vivo intracellular delivery to the DCs in comparison with controls after injection into tumor-bearing mice, and promoted DC maturation, leading to emergence of antigen-specific cytotoxic CD8+ T cells. Finally, the CH-NPs showed significantly greater antitumor efficacy in EG.7 and TC-1 tumor-bearing mice compared to the control (p < 0.01). Taken together, these data show that the CH-NP platform can be used as an immune response modulatory vaccine for active cancer immunotherapy without ex vivo manipulation, thus resulting in increased anticancer efficacy.
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Yeongseon
authors.initials: Y
authors.lastname: Byeon
authors.affiliation: Department of Dental Hygiene, Hanseo University, Seosan 31962, South Korea.
authors.forename: Jong-Hwa
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Hat Nim
authors.initials: HN
authors.lastname: Jeon
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Ga Hee
authors.initials: GH
authors.lastname: Kim
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Min Gi
authors.initials: MG
authors.lastname: Kim
authors.affiliation: Department of Convergence Medicine, University of Ulsan College of Medicine &Asan Institute for Life Sciences, Asan Medical Center, Seoul 055-05, South Korea.
authors.forename: Chan-Gi
authors.initials: CG
authors.lastname: Pack
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Tae Heung
authors.initials: TH
authors.lastname: Kang
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.affiliation: SKKU Advanced Institute of Nanotechnology (SAINT), School of Chemical Engineering, Sungkyunkwan University, Suwon 25-2, South Korea.
authors.forename: Yong Taik
authors.initials: YT
authors.lastname: Lim
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, Kwang-Jin-Gu, Seoul 143-747, South Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sunkyunkwan University School of Medicine, Seoul 06531, South Korea.
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Bio/Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, South Korea.
authors.forename: Byung Cheol
authors.initials: BC
authors.lastname: Shin
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, South Korea.
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Ahn
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, the University of Texas M.D. Anderson Cancer Center, Texas, USA.|Department of Cancer Biology, the University of Texas M.D. Anderson Cancer Center, Texas, USA.|Center for RNA Interference and Non-coding RNA, The University of Texas M.D. Anderson Cancer Center, Texas, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005260:Female; D015870:Gene Expression; D056747:Immunomodulation / Q000187:drug effects; D007167:Immunotherapy / Q000379:methods*; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008223:Lymphoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D011070:Poly I-C / Q000008:administration & dosage*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology; D014162:Transfection
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D019496:Cancer Vaccines; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D010047:Ovalbumin; D048271:Chitosan; D011070:Poly I-C