PSMA基因疫苗抑瘤效应及免疫机制的实验研究

目的： 观察表达前列腺特异性膜抗原(PSMA)基因疫苗在荷瘤小鼠模型中抑瘤效应并探讨其免疫机制，为前列腺癌的预防和免疫治疗提供实验基础。方法: 将PSMA基因疫苗肌注入BALB/c小鼠体内，检测其血清中PSMA抗体水平并观察脾T细胞的增殖效应和杀细胞毒效应，以sp2/0-PSMA细胞攻击免疫后小鼠，观察小鼠的成瘤率、肿瘤大小、平均瘤重及生存率，评价PSMA基因疫苗的抑瘤效应。结果: PSMA基因疫苗可诱导实验组小鼠产生PSMA抗体，脾T细胞的增殖效应和杀细胞毒效应，在一定时间内随着免疫次数的增加和时间的延长，抗体水平、脾细胞的增殖和杀细胞毒效应均呈上升趋势。与对照组相比较，实验组小鼠成瘤率低，无瘤生存期延长，肿瘤生长缓慢。结论: PSMA基因疫苗能诱导实验组小鼠产生特异性体液及细胞免疫应答，且有明显的抑瘤效应。

Anti-tumor efficacy and immune mechanism of gene vaccine expressing PSMA

AIM: To observe both the anti-tumor efficacy induced by gene vaccine expressing PSMA in mice and the feather of the specific immune responses, which may offer some theoretical knowledge and experimental foundation of the gene vaccine therapy for the prostate cancer.METHODS: pcDNA3.0-PSMA plasmids were injected into the hind-leg quadriceps muscle of the BALB/c mice. Anti-PSMA antibody was detected in sera of the animals. The proliferation and cytotoxicity of the spleen cells were observed. The immunized mice were inoculated subcutaneously in the right flank with sp2/0-PSMA cells. The anti-tumor efficacy of the gene vaccine was determined through the ratio of the tumor formation, tumor volume, tumor weight and the survival rate of immunized mice.RESULTS: High levels of anti-PSMA antibody were induced in the immunized mice. The splenocytes from vaccination group were stimulated to produce strong proliferative responses and significant cytotoxic T-cells (CTL) activity. Moreover, during a period of time, the antibody concentration, proliferation index and CTL activity appeared to go up as the time went by and the numbers of immunization increased. After DNA vaccine immunization, tumor occurrence decreased, the tumor-free time was prolonged and the growth velocity of tumor was markedly reduced (P<0.05).CONCLUSION: The humoral and cellular immunity is induced by PSMA gene vaccine. The anti-tumor efficacy in the immunized mice is produced strikingly.