Tumor regression by combined immunotherapy and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma

• Published in: Cancer science Vol. 94; no. 3; pp. 308 - 313
• Main Authors: Ito, Akira, Tanaka, Kouji, Kondo, Kazuyoshi, Shinkai, Masashige, Honda, Hiroyuki, Matsumoto, Kazuhiko, Saida, Toshiaki, Kobayashi, Takeshi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2003; Blackwell; John Wiley & Sons, Inc
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Colony-stimulating factor; Combined Modality Therapy; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Disease Models, Animal; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; HSP70 Heat-Shock Proteins - analysis; Hyperthermia; Hyperthermia, Induced; Immunotherapy; Immunotherapy - methods; Interleukin-2 - therapeutic use; Leukocytes (granulocytic); Liposomes; Macrophages; Magnetic fields; Magnetics; Magnetite; Medical sciences; Melanoma; Melanoma, Experimental - immunology; Melanoma, Experimental - pathology; Melanoma, Experimental - therapy; Mice; Mice, Inbred C57BL; Nanoparticles; Nodules; Pharmacology. Drug treatments; Recombinant Proteins; Surface charge; Survival; Time Factors; Tumor Cells, Cultured; Tumors; Antineoplastic agent; Nanoparticle; Spontaneous; Cytokine; Rodentia; Liposome; Malignant tumor; Vertebrata; Mammalia; Magnetic; Interleukin 2; Mouse; Polypeptide; Animal; Immunotherapy; B16-Melanoma; Established cell line; Combined treatment; Granulocyte macrophage colony stimulating factor; Induced hyperthermia
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2003.tb01438.x

Immunotherapy (IT) has become an accepted therapeutic modality. We previously reported that intracellular hyperthermia (IH) using magnetic nanoparticles induces antitumor immunity. We undertook these studies in order to study the combined effects of IT and IH on melanoma. Magnetite cationic liposomes (MCLs) have a positive surface charge and generate heat in an alternating magnetic field (AMF) due to hysteresis loss. MCLs were injected into a B16 melanoma nodule in C57BL/6 mice, which were subjected to AMF for 30 min. The temperature at the tumor reached 43°C and was maintained by controlling the magnetic field intensity. At 24 h after IH, interleukin‐2 (IL‐2) or granulocyte macrophage‐colony stimulating factor (GM‐CSF) was injected directly into the melanoma. Mice were divided into six groups: group I (control), group II (IH), group III (IL‐2), group IV (GM‐CSF), group V (IH+IL‐2), and group VI (IH+GM‐CSF). Complete regression of tumors was observed in mice of groups V and VI (75% (6/ 8) and 40% (4/10) of the mice, respectively), while no tumor regression was observed in mice of the other groups. This study supports the combined use of IT and IH using MCLs in patients with advanced malignancies. (Cancer Sci 2003; 94: 308–313)