热休克蛋白gp96肽复合物免疫治疗小鼠骨肉瘤的研究

HSPgp96-peptide complexes for anti-tumor immunity of mice with osteosarcoma

目的研究热休克蛋白gp96(HSPgp96)肽复合物体内外特异性抗肿瘤作用。方法采用51Cr释放法测定经HSPgp96肽复合物修饰的树突状细胞(DC)对细胞毒性T淋巴细胞(CTL)杀伤活性的影响,同时在骨肉瘤动物模型上观察HSPgp96肽复合物与修饰后的DC对骨肉瘤的生长状况及体内免疫水平的影响。结果HSPgp96肽复合物修饰的DC可激活小鼠脾淋巴细胞,后者能对人成骨肉瘤细胞系MG-63细胞进行特异性杀伤;HSPgp96肽复合物及修饰后的DC使IL-10表达水平明显降低,IFN-γ水平明显上升(P<0.01),能有效抑制体内肿瘤的生长。结论HSPgp96肽复合物能很好地修饰体外诱导获取的DC,使DC具有很强的体内外抗肿瘤作用。

Objective To investigate the specific anti-tumor immunity of HSPgp96-peptide complexes in vitro and in vivo. Methods Standard ^51Cr release assay was used to detect the influence of CTL cytotoxic activity induced by dendritic cells （DC） modified by HSPgp96-peptide complexes. The anti-tumor effect was examined when osteosarcoma animal model was treated with HSPgp96-peptide complexes and DC. Results DC modified by HSPgp96-peptide complexes could activate spleen lymphocytes and the latter could specifically kill osteosarcoma cells. HSPgp96-peptide complexes and modified DC could significantly reduce IL-10 level and elevate IFN-γ level P〈0. 01, then inhibiting tumor growth effectively. Conclusion HSPgp96- peptide complexes can activate DC effectively, making DC a good vaccine.