Yanase M, Shinkai M, Honda H, Wakabayashi T, Yoshida J, Kobayashi T
Department of Biotechnology, Graduate School of Engineering, Nagoya University.
Jpn J Cancer Res. 1998 Jul;89(7):775-82. doi: 10.1111/j.1349-7006.1998.tb03283.x.
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, immunocytochemical 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.
研究了使用功能性磁性颗粒通过细胞内热疗诱导对T-9大鼠胶质瘤的抗肿瘤免疫。具有正表面电荷的磁铁矿阳离子脂质体（MCLs）被用作细胞内热疗的加热介质。在雌性F344大鼠的双侧股骨皮下形成实体T-9胶质瘤组织，仅通过针头将MCLs注射到左侧实体肿瘤（治疗侧）中。然后将大鼠分为两组，一组不接受照射，另一组以24小时间隔给予交变磁场（118 kHz，384 Oe）照射30分钟，共照射三次。在治疗侧，许多暴露于磁场的大鼠的肿瘤组织完全消失。即使未将MCLs注射到右侧实体肿瘤中，对侧的肿瘤组织也完全消失。为了检查是否可以产生持久的肿瘤特异性免疫，对通过热疗治愈的大鼠在3个月后用T-9细胞再次进行攻击。经过一段时间的短暂生长后，所有肿瘤均消失。此外，免疫细胞化学分析显示，热疗诱导的免疫反应由CD8 +和CD4 + T细胞介导，并伴有肿瘤选择性细胞毒性T淋巴细胞活性的显著增强。这些结果表明，我们的磁性颗粒可能是实体肿瘤热疗的有效工具，因为除了通过热杀死肿瘤细胞外，还诱导了宿主免疫反应。
