title: Nanoparticles built by self-assembly of amphiphilic gamma-PGA can deliver antigens to antigen-presenting cells with high efficiency: a new tumor-vaccine carrier for eliciting effector T cells.
abstract: Nanotechnology is a fundamental technology for designing and generating innovative carriers for biomacromolecular drugs. Biodegradable poly(gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent vaccine carriers capable of delivering antigenic proteins to antigen-presenting cells (APCs) and eliciting potent immune responses based on antigen-specific cytotoxic T lymphocytes. In mice, subcutaneous immunization with gamma-PGA NPs entrapping ovalbumin (OVA) more effectively inhibited the growth of OVA-transfected tumors than immunization with OVA emulsified using Freund's complete adjuvant. In addition, gamma-PGA NPs did not induce histopathologic changes after subcutaneous injection or acute toxicity through intravenous injection. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins into APCs, and these antigen-capturing APCs migrated to regional lymph nodes. Our results demonstrate that a gamma-PGA NP system for antigen delivery will advance the clinical utility of vaccines against cancer.
authors.affiliation: Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Okada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Oda
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsuo
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsuo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kayamuro
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ishii
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Yoshinaga
authors.forename: Takami
authors.initials: T
authors.lastname: Akagi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nakagawa
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D045744:Cell Line, Tumor; D004337:Drug Carriers; D005620:Freund's Adjuvant / Q000494:pharmacology; D007150:Immunohistochemistry; D007167:Immunotherapy; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011099:Polyglutamic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015203:Reproducibility of Results; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004337:Drug Carriers; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D010047:Ovalbumin; D005620:Freund's Adjuvant