Immunogene therapy of tumors with vaccine based on Xenopus homologous vascular endothelial growth factor as a model antigen

Overcoming immune tolerance of the growth factors associated with tumor gro wth should be a useful approach to cancer therapy by active immunity. We us ed vascular endothelial growth factor (VEGF) as a model antigen to explore the feasibility of the immunogene tumor therapy with a vaccine based on a s ingle xenogeneic homologous gene, targeting the growth factors associated w ith angiogenesis. To test this concept, we constructed a plasmid DNA encodi ng Xenopus homologous VEGF (XVEGF-p) and control vectors. We found that imm unogene tumor therapy with a vaccine based on XVEGF was effective at both p rotective and therapeutic antitumor immunity in several tumor models in mic e. VEGF-specific autoantibodies in sera of mice immunized with XVEGF-p coul d be found in Western blotting analysis and ELISA assay. The purified immun oglobulins were effective at the inhibition of VEGF-mediated endothelial ce ll proliferation in vitro, and at antitumor activity and the inhibition of angiogenesis by adoptive transfer in vivo. The elevation of VEGF in the ser a of the tumor-bearing mice could be abrogated with XVEGF-p immunization. T he antitumor activity and production of VEGF-specific autoantibodies, signi ficantly elevated IgG1 and IgG2b, could be abrogated by the depletion of CD 4+ T lymphocytes. The observations may provide a vaccine strategy for cance r therapy through the induction of autoimmunity against the growth factors associated with tumor growth in a cross reaction with single xenogeneic hom ologous gene and may be of importance in the further exploration of the app lications of other xenogeneic homologous genes identified in human and othe r animal genome sequence projects in cancer therapy.