Antitumor Immunity Induction by Intracellular Hyperthermia Using Magnetite Cationic Liposomes

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Abstract
Induction of antitumor immunity to T‐9 rat glioma by intracellular hyperthermia using functional magnetic particles was investigated. Magnetite cationic liposomes (MCLs), which have a positive surface charge, were used as heating mediators for intracellular hyperthermia. Solid T‐9 glioma tissues were formed subcutaneously on both femurs of female F344 rats, and MCLs were injected via a needle only into the left solid tumors (treatment side). The rats were then divided into two groups, which received no irradiation, or irradiation for 30 min given three times at 24‐h intervals with an alternating magnetic field (118 kHz, 384 Oe). On the treatment side, the tumor tissue disappeared completely in many rats exposed to the magnetic field. The tumor tissue on the opposite side also disappeared completely, even though MCLs were not injected into the right solid tumors. To examine whether a long‐lasting and tumor‐specific immunity could be generated, the rats that had been cured by the hyperthermia treatment were rechallenged with T‐9 cells 3 months later. After a period of transient growth, all tumors disappeared. Furthermore, immuno‐cytochemical assay revealed that the immune response induced by the hyperthermia treatment was mediated by both CD8+ and CD4+ T cells and accompanied by a marked augmentation of tumor‐selective cytotoxic T lymphocyte activity. These results suggest that our magnetic particles are potentially effective tools for hyperthermic treatment of solid tumors, because in addition to killing of the tumor cells by heat, a host immune response is induced.