IL-21膜表面修饰MB49细胞疫苗治疗小鼠转移性膀胱癌的实验研究

目的制备白细胞介素21(IL-21)膜表面修饰的小鼠膀胱癌MB49细胞疫苗,评价其在小鼠膀胱癌皮下转移模型中诱导特异性细胞毒性T淋巴细胞(CTL s)的效应和治疗作用。方法将SA-IL-21锚定在经30%酒精灭活后的MB49细胞膜表面而制成IL-21膜表面修饰疫苗。建立C57BL/6小鼠皮下MB49膀胱癌模型,将荷瘤小鼠随机分为5组:IL-21膜表面修饰疫苗组、单纯游离IL-21组、GFP膜表面修饰疫苗组、单独灭活MB49肿瘤疫苗组、PBS组。利用上述制备的疫苗进行治疗,通过检测各组小鼠肿瘤体积变化及CTL来评价疫苗的抗肿瘤功能。结果成功制备了IL-21膜表面修饰MB49疫苗。IL-21/MB49疫苗可显著抑制肿瘤生长并产生长期特异性免疫反应(P<0.05)。在同一效靶比下IL-21/MB49疫苗组的CTL杀伤活性显著高于其他组(P<0.05)。结论采用蛋白膜锚定技术可将IL-21高效锚定于MB49细胞膜表面制备成IL-21膜表面修饰膀胱癌肿瘤疫苗,该疫苗既可保持IL-21生物学活性又可明显增强CTL杀伤BCa肿瘤活性。

Interleukin-21 surface-modified MB49 cell vaccine for treatment of metastatic bladder in mice

Objective To develop a novel vaccine by immobilizing interleukin-21(IL-21) on the surface of MB49 cells and evaluate its effect in inducing specific cytotoxic T lymphocytes(CTLs) and antitumor immunity in a mouse model of subcutaneous metastatic bladder cancer.Methods SA-IL-21 was immobilized on the surface of 30% ethanol-fixed MB49 cells to prepare the cell vaccine.C57BL/6 mice with subcutaneous implantation of MB49 bladder cancer cells were randomized into 5 groups to receive treatments with IL-21/MB49 vaccine,soluble IL-21,GFP surface-modified MB49 cells,ethanol-fixed MB49 cells,or PBS.The tumor growth and CTL were examined to assess the antitumor efficacy of the vaccine.Results IL-21 surface-modified MB49 cell vaccine significantly inhibited the tumor growth and generated a long-lasting memory response(P<0.05).At the same effector-target(E:T) ratio,the specific CTLs induced by IL-21/MB49 vaccine showed the most potent cytotoxicity against MB49 cells(P<0.05).Conclusion With the protein-anchor technique,IL-21 can be efficiently immobilized on the surface of MB49 cells to prepare IL-21/MB49 cells vaccine.The novel vaccine can maintain its biological activity and significantly enhance the cytotoxicity of CTLs against bladder cancer cells.