title: Toll-like receptor 3-induced immune response by poly(d,l-lactide-co-glycolide) nanoparticles for dendritic cell-based cancer immunotherapy.
abstract: Dendritic cells (DCs) are potent professional antigen-presenting cells that are capable of initiating a primary immune response and activating T cells, and they play a pivotal role in the immune responses of the host to cancer. Prior to antigen presentation, efficient antigen and adjuvant uptake by DCs is necessary to induce their maturation and cytokine generation. Nanoparticles (NPs) are capable of intracellular delivery of both antigen and adjuvant to DCs. Here, we developed an advanced poly(d,l-lactide-co-glycolide) (PLGA)-NP encapsulating both ovalbumin (OVA) as a model antigen and polyinosinic-polycytidylic acid sodium salt (Toll-like receptor 3 ligand) as an adjuvant to increase intracellular delivery and promote DC maturation. The PLGA-NPs were taken up by DCs, and their uptake greatly facilitated major histocompatibility class I antigen presentation in vitro. Moreover, vaccination with PLGA-NP-treated DCs led to the generation of ovalbumin-specific CD8+T cells, and the resulting antitumor efficacy was significantly increased in EG.7 and TC-1 tumor-bearing mice compared to control mice (P<0.01). Taken together, these findings demonstrated that the PLGA-NP platform may be an effective method for delivering tumor-specific antigens or adjuvants to DCs.
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungwondaero, Chungju-Si, Chungcheongbuk-Do.
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungwondaero, Chungju-Si, Chungcheongbuk-Do.
authors.forename: Yeongseon
authors.initials: Y
authors.lastname: Byeon
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungwondaero, Chungju-Si, Chungcheongbuk-Do.
authors.forename: Tae Heung
authors.initials: TH
authors.lastname: Kang
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungwondaero, Chungju-Si, Chungcheongbuk-Do.
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Bio/Drug Discovery Division, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon.
authors.forename: Byung Cheol
authors.initials: BC
authors.lastname: Shin
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, Kwang-Jin-Gu, Seoul, South Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine; Department of Cancer Biology; Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, TX, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungwondaero, Chungju-Si, Chungcheongbuk-Do.
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007167:Immunotherapy; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010047:Ovalbumin / Q000276:immunology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013945:Thymoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013953:Thymus Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051196:Toll-Like Receptor 3 / Q000276:immunology* / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D051196:Toll-Like Receptor 3; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin
keywords: PLGA nanoparticles; antigen delivery; cancer immunotherapy