Tumor regression by combined immunotherapy and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma.
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 degrees 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.
Ito
Akira
A
Department of Biotechnology, School of Engineering, Nagoya University.
Tanaka
Kouji
K
Kondo
Kazuyoshi
K
Shinkai
Masashige
M
Honda
Hiroyuki
H
Matsumoto
Kazuhiko
K
Saida
Toshiaki
T
Kobayashi
Takeshi
T
D000818:Animals; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D006979:Hyperthermia, Induced; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000627:therapeutic use; D008280:Magnetics; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins; D013534:Survival; D013997:Time Factors; D014407:Tumor Cells, Cultured
D018840:HSP70 Heat-Shock Proteins; D007376:Interleukin-2; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor