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Antitumor Immunity Induction by Intracellular Hyperthermia Using Magnetite Cationic Liposomes

机译:磁铁矿阳离子脂质体通过细胞内热疗诱导抗肿瘤免疫。

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摘要

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.
机译:研究了使用功能性磁性粒子通过细胞内热疗诱导对T-9大鼠神经胶质瘤的抗肿瘤免疫力。具有正表面电荷的磁铁矿阳离子脂质体(MCL)用作细胞内热疗的加热介质。在雌性F344大鼠的两个股骨下皮下均形成了T-9胶质瘤实体组织,仅通过针头将MCL注射到左侧的实体瘤中(治疗侧)。然后将大鼠分为两组,不接受任何照射,或以交变磁场(118 kHz,384 Oe)以24-h的间隔每3次照射30分钟。在治疗方面,在许多暴露于磁场的大鼠中,肿瘤组织完全消失。即使未将MCL注入正确的实体瘤中,另一侧的肿瘤组织也完全消失。为了检查是否可以产生持久且具有肿瘤特异性的免疫力,在3个月后用T-9细胞对通过高温治疗治愈的大鼠进行再攻击。经过一段时间的短暂生长,所有肿瘤均消失。此外,免疫细胞化学分析显示,高热治疗诱导的免疫应答是由CD8 + 和CD4 + T细胞介导的,并伴随着肿瘤的明显增加。选择性的细胞毒性T淋巴细胞活性。这些结果表明,我们的磁性颗粒可能是对实体瘤进行高温治疗的潜在有效工具,因为除了通过加热杀死肿瘤细胞外,还可以诱导宿主免疫应答。

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