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

• Published in: Cancer science Vol. 101; no. 9; pp. 1939 - 1946
• Main Authors: Sato, Akiko, Tamura, Yasuaki, Sato, Noriyuki, Yamashita, Toshiharu, Takada, Tomoaki, Sato, Makito, Osai, Yasue, Okura, Masae, Ono, Ichiro, Ito, Akira, Honda, Hiroyuki, Wakamatsu, Kazumasa, Ito, Shosuke, Jimbow, Kowichi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-2010; Blackwell
• Subjects: Animals; Biological and medical sciences; Cell Line, Tumor; Cross-Priming - immunology; Cystamine - analogs & derivatives; Cystamine - chemistry; Cytotoxicity, Immunologic - immunology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dermatology; Electromagnetic Fields; Female; Heat-Shock Proteins - immunology; Heat-Shock Proteins - metabolism; Hot Temperature; HSP72 Heat-Shock Proteins - immunology; HSP72 Heat-Shock Proteins - metabolism; Hyperthermia, Induced; Magnetite Nanoparticles - administration & dosage; Magnetite Nanoparticles - chemistry; Magnetite Nanoparticles - therapeutic use; Medical sciences; Melanoma, Experimental - immunology; Melanoma, Experimental - pathology; Melanoma, Experimental - therapy; Mice; Mice, Inbred C57BL; Original; Peptides - immunology; Peptides - metabolism; Phenols - chemistry; Protein Binding; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes, Cytotoxic - immunology; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Cancerology; Magnetite; Treatment; Peptides; Nanoparticle; Targeted therapy; Malignant melanoma; Heat shock protein; Malignant tumor; Cytotoxic T lymphocyte; Cancer
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/j.1349-7006.2010.01623.x

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. (Cancer Sci 2010)