title: Melanoma-targeted chemo-thermo-immuno (CTI)-therapy using N-propionyl-4-S-cysteaminylphenol-magnetite nanoparticles elicits CTL response via heat shock protein-peptide complex release.
abstract: Melanogenesis substrate, N-propionyl-4-S-cysteaminylphenol (NPrCAP) is specifically taken up by melanoma cells and inhibits their growth by producing cytotxic free radicals. By taking advantage of this unique chemical agent, we have established melanoma-targeting intracellular hyperthermia by conjugating NPrCAP with magnetite nanoparticles (NPrCAP/M) upon exposure to an alternating magnetic field (AMF). This treatment causes cytotoxic reaction as well as heat shock responses, leading to elicitation of antitumor immune response, which was proved by tumor rechallenge test and CTL induction. We found the level of heat shock protein 72 (Hsp72) to be increased in the cell lysate and culture supernatant after intracellular hyperthermia. Melanoma-specific CD8(+) T-cell response to dendritic cells loaded with hyperthermia-treated tumor lysate was enhanced when compared with non-treated tumor lysate. When heat shock protein, particularly Hsp72, was immuno-depleted from hyperthermia-treated tumor cell lysate, specific CD8(+) T-cell response was abolished. Thus, it is suggested that antitumor immune response induced by hyperthermia using NPrCAP/M is derived from the release of HSP-peptide complex from degraded tumor cells. Therefore, this chemo-thermo-immuno (CTI)-therapy might be effective not only for primary melanoma but also for distant metastasis because of induction of systemic antimelanoma immune responses.
authors.affiliation: Department of Dermatology, Faculty of Engineering, Kyusyu University, Fukuoka, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sato
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamashita
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Takada
authors.forename: Makito
authors.initials: M
authors.lastname: Sato
authors.forename: Yasue
authors.initials: Y
authors.lastname: Osai
authors.forename: Masae
authors.initials: M
authors.lastname: Okura
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ono
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honda
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Shosuke
authors.initials: S
authors.lastname: Ito
authors.forename: Kowichi
authors.initials: K
authors.lastname: Jimbow
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D045142:Cross-Priming / Q000276:immunology; D003538:Cystamine / Q000031:analogs & derivatives* / Q000737:chemistry; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004574:Electromagnetic Fields; D005260:Female; D050884:HSP72 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D006358:Hot Temperature; D006979:Hyperthermia, Induced; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D010636:Phenols / Q000737:chemistry*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D058185:Magnetite Nanoparticles; C114098:N-propionyl-4-S-cysteaminylphenol; D010455:Peptides; D010636:Phenols; D003538:Cystamine