The formation of new capillaries from pre-existing vessels, angiopoiesis, is correlated to the invasion, growth and metastasis of solid tumors. Anti-angiogenic therapy, which targets activated endothelial cells, has been an important alternative for the treatment of tumors. The present study provides a navel strategy for achieving an antitumor immune response with a DNA vaccine including the multitarget complex antigen. VEGF-E, VEGF-R2 and αVβ3 were selected as targets to inhibit the growth of tumor, and 3 heterogeneity antigens, each of which involving at least two of Mus musculus, orf virus, Quail, homo-sapiens and Xenopus laevis, were designed. At the same time, VEGF-E, VEGF-R2 and αVβ3 were fused together to produce a multitarget complex antigen, ERV.Balb/c mice were immunized by the DNA vaccines including complex antigens above-mentioned. we found that favourable humoral immunoresponse was induced and the maximum of titer antibody, especially in mice immunized with ERV, is to 1:10000. Meanwhile, specific cellullar immunologic response was induced, the ratio of CD4+/CD8+ increased and specific T cell response such as IFN-γ and IL-4 release was much increased in complex antigen groups than in the control groups. In immunized mice, the protective effect against transgenic RenCa cells, such as inhibition of tumor growth and prolonging the lifespan can be observed. The time of tumor forming in ERV group was longer than the control groups(89 days), to about 19days; and the survival rate of mice increased to 83% and 33% in control groups; and the tumor control rate was 95.36% (the weight of tumors was 0.20±0.16g in the group of ERV, while 5.09±0.33g and 5.93±0.96g in control groups).At the same time, G250-MN/CA IX was cloned cloned from RCC and DNA vaccine thereof was constructed successfully. Our findings may be the foundation of the tumor therapy by combining tumor specific antigen and anti-angiogenic antigen.
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