title: Heat shock protein 70 expression induces antitumor immunity during intracellular hyperthermia using magnetite nanoparticles.
abstract: In this study we demonstrated that heat shock protein (HSP) 70 expression by hyperthermia induced antitumor immunity in the T-9 rat glioma. Our hyperthermic system using magnetic nanoparticles induced necrotic cell death that correlated with HSP70 expression. We purified the HSP70-peptide complexes from the tumor after hyperthermia to investigate whether HSP70 was involved in the antitumor immunity, and we found that in the F344 rats immunized with T-9-derived HSP70 the tumor growth of T-9 was significantly suppressed. Tumor rejection assay after hyperthermic treatment of implanted T-9 cells with incorporated magnetite cationic liposomes (MCL) was performed to investigate whether antitumor immunity was induced by release of HSP70 from the necrotic cells in the F344 rat. Tumor growth was strongly suppressed in the rats subjected to hyperthermia of implanted T-9 cells, and 50% of rats were protected from challenge with T-9 cells. Immunogenicity was enhanced when the HSP70-overexpressing T-9 cells were killed via necrosis in rats by hyperthermia, after which all rats were completely protected from challenge with T-9 cells. Our hyperthermic system produces vaccination with HSP70-peptide via necrotic tumor cell death in vivo, resulting in antitumor immunity. This phenomenon, which may be termed in situ vaccination, has important implications for the development of novel antitumor therapies.
authors.affiliation: Department of Biotechnology, School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.forename: Masashige
authors.initials: M
authors.lastname: Shinkai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Saga
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Wakabayashi
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D002412:Cations; D005260:Female; D052203:Ferrosoferric Oxide; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006979:Hyperthermia, Induced / Q000379:methods*; D007501:Iron / Q000008:administration & dosage*; D008081:Liposomes; D009336:Necrosis; D010087:Oxides / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002412:Cations; D018840:HSP70 Heat-Shock Proteins; D008081:Liposomes; D010087:Oxides; D007501:Iron; D052203:Ferrosoferric Oxide