特异性表达Her-2抗原树突状细胞疫苗治疗非小细胞性肺癌体外抗瘤效应的研究

In Vitro Antitumor Study of Specific Expression of Her-2 Antigen Dendritic Cell Vaccine in the Treatment of Non-small Cell Lung Cancer

目的探索特异性表达人表皮生长因子受体2(human epidermal growth factor receptor 2,Her-2)抗原的树突状细胞疫苗(dendritic cell,DC)诱导淋巴细胞活化增殖能力和其治疗非小细胞性肺癌的免疫效应。方法构建表达Her-2基因的慢病毒载体(lentivirus vectors,LV),制备3组疫苗:LV-Her2-DC、LV-DC、单纯DC,评估其安全性并比较三组疫苗分别诱导淋巴细胞增殖情况及其对非小细胞性肺癌的细胞的杀伤能力。结果LV-Her2-DC诱导CIK活化增殖能力约为LV-DC和单纯DC的2倍(P=0.00)。其中,LV-DC和单纯DC诱导CIK增殖能力无明显差异(P=0.06),LV-Her2-DC诱导CIK增殖能力明显强于单纯DC组(P=0.007)。LV-Her2-DC-CIK对表达Her-2的肿瘤细胞株杀伤率明显高于单纯DC-CIK组(P<0.05),LV-DC-CIK空载体组与单纯DC-CIK对照组的杀瘤率相比无统计学差异(P>0.05)。结论以慢病毒为载体转染DC,特异性表达Her-2的DC疫苗诱导CIK增殖活化能力和治疗非小细胞性肺癌的效应明显增强,为肿瘤的转化治疗提供了一定的实验和理论基础。

Objective To explore the ability of dendritic cell vaccine expressing HER-2 induced CIK proliferation and anti-tumor immune responses on non-small cell lung cancer.Methods Construction of full-length Her-2 gene containing lenti-virus vector(LV-Her2)was made.Preparation of DCs transducer with LV-Her2(LV-Her2-DC)as the experimental group,DCs transducer with empty vector(LV-DC)and untreated DCs were used as controls.To evaluate the safety and compare the ability of inducing lymphocyte proliferation and antitumor effect in the 3 DCs vaccines.Results The activation and proliferation capacity of CIK co-culture with LV-Her2-DC was about twice than the empty vector DCs and untreated DCs(P=0.00),the proliferation of CIK co-culture with empty vector DCs and untreated DCs had no significant difference(P=0.06),the proliferation of CIK coculture with LV-Her2-DC was significantly higher than untreated DC(P=0.007).LV-Her2-DC-CIK markedly enhanced the antitumor effect than DC-CIK(P<0.05),but there was no significant difference between LV-DC-CIK and DC-CIK(P>0.05).Conclusion We successfully constructed a recombinant lentiviral vector encoding the Her-2 gene which could effectively induce Her-2 expression in DCs.The activation and proliferation capacity of CIK transduced with LV-Her2-DCs is markedly enhanced.The anti-tumor effect is stronger than LV-DC-CIK and DC-CIK.This study made a certain experimental and theoretical basis to develop an innovating individualized treatment for patients.