ANTITUMOR IMMUNITY INDUCTION BY INTRACELLULAR HYPERTHERMIA USING MAGNETITE CATIONIC LIPOSOMES

Induction of antitumor immunity to T-9 rat glioma by intracellular hyp erthermia using functional magnetic particles was investigated, Magnet ite cationic liposomes (MCLs), which have a positive surface charge, w ere used as heating mediators for intracellular hyperthermia. Solid T- 9 glioma tissues were formed subcutaneously on both femurs of female F 344 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 t imes at 24-h intervals with an alternating magnetic field (118 kHz, 35 4 Oe), On the treatment side, the tumor tissue disappeared completely in many rats exposed to the magnetic field, The tumor tissue on the op posite side also disappeared completely, even though MCLs were not inj ected into the right solid tumors. To examine whether a long-lasting a nd 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 disappea red. Furthermore, immunocytochemical assay revealed that the immune re sponse induced by the hyperthermia treatment was mediated by both CD8( +) and CD4(+) T cells and accompanied by a marked augmentation of tumo r-selective cytotoxic T lymphocyte activity. These results suggest tha t our magnetic particles are potentially effective tools for hyperther mic treatment of solid tumors, because in addition to killing of the t umor cells by heat, a host immune response is induced.