Development of systemic antitumor effect against malignant glioma by local convection-enhanced delivery

本研究的目的是通过新的给药系统，即对流增强给药系统，通过局部给药来发展全身免疫。首先，我们分析了化疗药物CED对脑组织的影响；ACNU。注射安全剂量的ACNU后，血脑屏障瞬间打开。基于这一发现，我们尝试用阿霉素脂质体与ACNU的CED联合全身化疗治疗啮齿动物脑肿瘤模型。这种治疗方法延长了模型的存活时间。因此，我们测试了编码OX-40蛋白的腺病毒局部CED递送诱导全身免疫的能力。采用鼠脑肿瘤模型观察该策略的抗肿瘤效果。

This study was started with the aim to develop systemic immunity by locally delivering agents with novel drug delivery system, i.e. convection-enhanced delivery. First, we analyzed the changes in brain tissue that received CED of chemotherapeutic agent ; ACNU. Transient opening of the Blood-brain barrier was noted with the delivery of ACNU at safety dose. With this finding, we tried to combine systemic chemotherapy using liposomal doxorubicin with CED of ACNU to treat rodent brain tumor model. Prolonged survival of the model was noted with this treatment. Consequently, we tested the ability of local CED delivery of adenovirus encoding OX-40 protein to induce systemic immunity. With this strategy antitumor efficacy was observed using rodent brain tumor model.