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目的研究C型CpG单链寡脱氧核苷酸(CpG ODN)对肿瘤疫苗抑瘤效果的增强作用。方法利用体外淋巴细胞增生实验和病毒保护实验确定新C型CpG ODN,采用小鼠体内抑瘤实验观察CpG ODN对肿瘤疫苗HSP65-MUC1重组蛋白抑制MUC1阳性肿瘤生长的增强作用,并对小鼠血清中抗HSP65-MUC1抗体的类型进行了初步鉴定。结果自行设计的CpG ODN BW005能刺激人PBMC和小鼠脾细胞增生,其刺激后的培养上清具有保护Vero E6细胞免受VSV感染的作用,属于新型C型CpG ODN。将BW005与HSP65-MUC1联合应用于C57BL/6小鼠后,MUC1阳性肿瘤的发生明显延缓(平均44.8d),其终末肿瘤发生率最低(33.33%);荷瘤小鼠的生存期明显延长(平均49.5d),其终末生存率最高(66.67%)。小鼠血清中抗HSP65和抗MUC1的IgG2a抗体水平增加。结论C型CpG ODN可以增强肿瘤疫苗HSP65-MUC1的抑瘤效果,考虑与小鼠体内Th1环境的形成有关。
Objective To study the anti-tumor effect of CpG ODN on tumor vaccine. Methods The new C-type CpG ODN was determined by in vitro lymphoproliferation and virus protection experiments. CpG ODN in vivo was used to observe the anti-tumor effect of CpG ODN on the growth of MUC1 -positive tumor cells. The type of anti-HSP65-MUC1 antibody was preliminarily identified. Results The designed CpG ODN BW005 stimulated the proliferation of splenocytes in human PBMCs and mice. The stimulated culture supernatant had the protective effect on Vero E6 cells from VSV infection and belonged to the novel C-type CpG ODN. The combined application of BW005 and HSP65-MUC1 in C57BL / 6 mice delayed the development of MUC1-positive tumors (average 44.8 days), with the lowest incidence of terminal tumors (33.33%). The survival of tumor-bearing mice was significantly prolonged (Average 49.5 days), the highest survival rate (66.67%). IgG2a antibody levels against HSP65 and anti-MUC1 in mouse sera increased. Conclusion C-type CpG ODN can enhance the anti-tumor effect of tumor vaccine HSP65-MUC1, which may be related to the formation of Th1 environment in mice.