Tan Guang-Hong, Li Yue-Nan, Huang Feng-Ying, Wang Hua, Bai Rui-Zhen, Jang Jie
Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou, People's Republic of China.
Immunol Invest. 2007;36(4):423-40. doi: 10.1080/08820130701361103.
The immunization approaches with DNA vaccine priming and subsequent protein or peptide boosting has been widely tested in various models of infectious diseases. However, these approaches are seldom reported in the areas of cancer immunotherapy. In this study we combined endoglin plasmid DNA and recombinant protein as vaccines and used them to prime and boost, simultaneously, as a vaccine strategy. Our results showed that combination of endoglin DNA and protein vaccines could enhance both protective and therapeutic anti-tumor efficacy in both colon carcinoma and Lewis lung carcinoma models. Significant inhibition of tumor angiogenesis was found in the tumor tissues. The titers of autoantibodies against murine endoglin were significantly increased and the antibody levels lasted longer in the mice with combined endoglin DNA and recombinant protein vaccination. CTL response against endoglin-positive HUVECs, but not against endoglin-negative tumor cells was found in the mice combined DNA with protein vaccination. In addition, combination of endoglin DNA and recombinant protein vaccination significantly induced IFN-gamma secreting cells. These observations suggested that a combination of endoglin DNA and recombinant protein immunization as a vaccine strategy was superior to those using endoglin DNA or recombinant protein alone as vaccines.
采用DNA疫苗初免并随后用蛋白质或肽加强免疫的方法已在各种传染病模型中得到广泛测试。然而,这些方法在癌症免疫治疗领域鲜有报道。在本研究中,我们将内皮糖蛋白质粒DNA和重组蛋白组合作为疫苗,并将它们同时用于初免和加强免疫,作为一种疫苗策略。我们的结果表明,内皮糖蛋白DNA和蛋白质疫苗的组合在结肠癌和Lewis肺癌模型中均可增强保护性和治疗性抗肿瘤疗效。在肿瘤组织中发现肿瘤血管生成受到显著抑制。在接受内皮糖蛋白DNA和重组蛋白联合疫苗接种的小鼠中,抗小鼠内皮糖蛋白自身抗体的滴度显著升高,且抗体水平持续时间更长。在DNA与蛋白质联合疫苗接种的小鼠中,发现了针对内皮糖蛋白阳性人脐静脉内皮细胞(HUVEC)的细胞毒性T淋巴细胞(CTL)反应,但未发现针对内皮糖蛋白阴性肿瘤细胞的CTL反应。此外,内皮糖蛋白DNA和重组蛋白联合疫苗接种显著诱导了分泌γ干扰素的细胞。这些观察结果表明,内皮糖蛋白DNA和重组蛋白联合免疫作为一种疫苗策略优于单独使用内皮糖蛋白DNA或重组蛋白作为疫苗的策略。