A comparative study of gene vaccines encoding different extracellular domains of the vascular endothelial growth factor receptor 2 in the mouse model of colon adenocarcinoma CT-26
A comparative study of gene vaccines encoding different extracellular domains of the vascular endothelial growth factor receptor 2 in the mouse model of colon adenocarcinoma CT-26
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DOI：
10.4161/cbt.7.4.5477
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发表时间：
2008-04-01
影响因子：
3.6
通讯作者：
Li, Miao
中科院分区：
文献类型：
--
作者：
Dong, Jian;Yang, Jun;Li, Miao
目的：比较编码VEGFR 2胞外区1-4域的基因疫苗的免疫原性和抗肿瘤效果。结果：两种DNA疫苗均能降低VEGF水平，提高特异性抗体，免疫小鼠淋巴细胞亚群维持较高水平，肿瘤潜伏期和存活时间延长，免疫小鼠的免疫原性和抗肿瘤效果均优于对照组。肿瘤体积、重量、MVD及肝转移均明显小于对照组。分别用编码胞外1-4和全长VEGFR 2的基因疫苗口服免疫CT-26结肠腺癌小鼠模型。通过检测肿瘤体积、小鼠生存时间、肿瘤内微血管密度（MVD）及肝转移情况评价其抗肿瘤作用。为探讨口服基因疫苗的合理作用机制，采用ELISA法检测血清中VEGF和抗VEGFR 2抗体水平，流式细胞仪和免疫组化法分别检测外周血和皮下肿瘤中CD 4+和CD 8 + T细胞。与全长VEGFR 2胞外区相比，VEGFR 2的胞外区1-4足以降低血清VEGF水平并特异性抑制肿瘤生长和转移。
Aims: To compare the immunogenicity and anti-tumor effects of gene vaccines encoding domains 1-4 with full length of extracellular region of VEGFR2.Results: Both DNA vaccines decreased VEGF levels and rose specific antibodies; the lymphocyte subsets of vaccinated mice maintained high; tumor latency period and survival time of immunized mice were prolonged; tumor size, weight, MVD and liver metastases were significantly less than the control groups.Methods: Mouse model of CT-26 adenocarcinoma of colon were treated with orally immunized gene vaccine encoding extracellular 1-4 and full length of VEGFR2 respectively. The effect of anti-tumor was evaluated by detecting the tumor volume, mice survival time, intratumoral microvessel density (MVD) and liver metastases. To explore the reasonable mechanism of the oral gene vaccines, the levels of VEGF and anti-VEGFR2 antibody in serum were detected by ELISA, CD4(+) and CD8(+) T cells in peripheral blood and subcutaneous tumors were analyzed by flow cytometer and immunohischemistry respectively.Conclusion: Compared with full length of extracellular domain of VEGFR2, extracellular regions 1-4 of VEGFR2 has been sufficient to decrease the serum VEGF level and to inhibit tumor growth and metastasis specifically.