The Affiliated Hospital of Medical College, Qingdao University, Shandong, PR China.
Hum Vaccin Immunother. 2012 Oct;8(10):1376-81. doi: 10.4161/hv.21321. Epub 2012 Aug 16.
Gene-modified cell vaccines are the best way to achieve the immunotherapy for all types of acute leukemia. In this study, the recombinant eukaryotic expression vector (pDisplay-HSP70) of heat shock protein 70 (HSP70) of Bacille Calmette-Guérin (BCG) was constructed by amplifying the whole BCG HSP70 gene using polymerase chain reaction (PCR) and sub-cloning into the polyclone endonuclease sites in pDisplay. Then the HL-60 cell vaccine expressing the protein onto the cell surface was prepared by lipofectamine transfection and its anti-tumor effect and mechanism were further studied. Results showed that the fragment of BCG HSP70 was consistent with Mycobacterium tuberculosis HSP70 gene published in GeneBank. DNA sequencing showed that the recombinant vector was correctly constructed and named pDisplay-HSP70. After BCG HSP70 gene transfection, the yellow-green fluorescence on the HL-60 cells surface was observed under a fluorescence microscope. The immunogenicity of HSP70-transfected HL-60 cells exhibited upregulated proliferation of lymphocytes, increased cytokine secretion (IFN-γ) and enhanced killing activity. These results suggested that gene transfection of BCG HSP70 could significantly enhance the immunogenicity of HL-60 cells. It may be used as a suitable candidate gene-modified cell vaccine for cancer immunotherapy.
基因修饰细胞疫苗是实现各种类型急性白血病免疫治疗的最佳方法。在这项研究中,通过聚合酶链反应(PCR)扩增卡介苗(BCG)的全长 HSP70 基因,并将其亚克隆到 pDisplay 的多克隆内切酶位点,构建了热休克蛋白 70(HSP70)的重组真核表达载体(pDisplay-HSP70)。然后,通过脂质体转染制备表达该蛋白的 HL-60 细胞疫苗,并进一步研究其抗肿瘤作用和机制。结果表明,BCG HSP70 片段与 GeneBank 中公布的结核分枝杆菌 HSP70 基因一致。DNA 测序表明,重组载体构建正确,命名为 pDisplay-HSP70。BCG HSP70 基因转染后,荧光显微镜下观察到 HL-60 细胞表面呈现黄绿色荧光。HSP70 转染的 HL-60 细胞的免疫原性表现为淋巴细胞增殖增加、细胞因子分泌(IFN-γ)增加和杀伤活性增强。这些结果表明,BCG HSP70 的基因转染可以显著增强 HL-60 细胞的免疫原性。它可能被用作癌症免疫治疗的合适候选基因修饰细胞疫苗。