Immunogene Therapy Of Tumors With Protein Vaccine Based On Chicken Homologous Tie-2

Angiogenesis is important for the growth of solid tumors. Overcoming immune tolerance of the growth factors associated with angiogenesis should be a useful approach to cancer therapy by active immunity. Tie2 (a.k.a Tek) is an endothelium-specific receptor tyrosine kinase known to play a role in tumor angiogenesis. In this study, we constructed a chicken homologous tie-2 protein vaccine(chTie-2) and a mouse tie-2 protein vaccine (mTie-2) as a control.. We found that immunogene tumor therapy with chTie-2 vaccine was effective at both protective and therapeutic antitumor immunity in two mouse tumor models(murine B16F10 melanoma, murine H22 hepatoma). Autoantibodies against mTie-2 were found in sera of mice immunized with chTie-2 in Western blotting analysis and ELISA assay. Histological examination revealed that the autoantibody was deposited on the endothelial cells within tumor tissues from chTie-2-immunized mice . Anti- Tie-2 antibody producing B cells were detectable by ELISPOT. The antitumor activity and production of autoantibodies against Tie-2 could be abrogated by depletion of CD4+ T lymphocytes. By adoptive transfer purified immunoglobulins in vivo, we found the antitumor activity and the inhibition of angiogenesis in the two mouse tumor models. In vitro the purified immunoglobulins could induce apoptosis of HUEVC (Human umbilical endothelial vein cell) . Angiogenesis was apparently inhibited within thetumors, and the vascularization of alginate beads was also reduced.. No observed side effect was found in the immunized mice. This study uses a vaccine strategy for cancer therapy through the induction of autoimniunity against the growth factor receptor associated with angiogenesis in a cross reaction with single xenogeneic homologous protein and demonstrates the potential utility of gene therapy of an antiangiogenic agent targeting an endothelium specific receptor, Tie2.