用脂质体包裹重组survivin腺病毒治疗肿瘤的实验研究

Anti-tumor Effects of Recombinant Adenovirus Encoding Survivin Encapsulated in Cationic Liposome

目的本实验拟用脂质体包裹重组survivin腺病毒治疗肿瘤,观察其抗肿瘤效应。方法在BALB/c小鼠建立CT26结肠癌模型,将小鼠随机分成用脂质体包裹重组survivin腺病毒组、重组survivin腺病毒组、用脂质体包裹空病毒组、脂质体组、PBS对照组5组,观察肿瘤的生长以及小鼠的存活情况和不良反应,并做细胞毒T淋巴细胞(CTL)分析。HE染色观察肿瘤组织及肿大淋巴结的病理改变。结果1用脂质体包裹重组survivin腺病毒对小鼠有免疫保护和治疗作用,小鼠肿瘤生长受到明显抑制,肿瘤大小和存活率与其它组比较,差异均有统计学意义(P<0.05)。2肿瘤病理切片显示用脂质体包裹重组survivin腺病毒组肿瘤组织内有较多的淋巴细胞浸润,有大量的坏死灶。3CTL分析显示用脂质体包裹重组survivin腺病毒组免疫小鼠的T细胞具有较高的CT26细胞杀伤活性,并具有特异性及不依赖NK细胞活性。结论用脂质体包裹重组survivin腺病毒对CT26移植瘤有治疗作用。

Objective To explore the anti-tumor effects and mechanisms of recombinant adenovirus encoding survivin encapsulated in cationic liposome. Methods CT26 tumor model was established in BALB/c mice. Fifty mice were randomly divided into five groups, including the group treated with recombinant adenovirus encoding survivin encapsulated in cationic liposome （Lip＋Ad-sur）, the group of recombinant adenovirus encoding survivin （Ad-sur）, the group of recombinant adenovirus encoding null encapsulated in cationic liposome（Lip＋Ad- null）, the group of liposome （Lip）, and the group of PBS alone （PBS）. Survival rate of mice, tumor volume, and side effects of treatments were observed. Lymphocytes were activated by adenovirus vaccine to kill tumor cells in vitro and in vivo. CTL assay and histological examination were carried out. Results Immunotherapy with recombinant adenovirus encoding survivin encapsulated in cationic liposome was effective for inducing protective and therapeutic anti-tumor immunity in CT26 tumor model. In the combination therapy group, the tumor growth was inhibited and the tumor volume was significantly smaller when compared with the controls. The survival rate of mice in the combination therapy group at 7 weeks after inoculation of tumor cells was significantly higher than that of the control group. Histologically, the tumor tissue was markedly necrotic and was infiltrated by lymphocytes. ^51Cr assay in vitro indicated that the combination therapy group showed higher specific killing activity against CT26 tumor cells than did the control groups, and the T cells were independent of NK cells. Conclusion Immunotherapy with recombinant adenovirus encoding survivin encapsulated in cationic liposome was noted to have a significant anti-tumor effect on CT26 tumor model.