Immunotherapy of tumors with protein vaccine based on chicken homologous Tie-2.
PURPOSE: Tie-2 is an endothelium-specific receptor tyrosine kinase known to play a key role in tumor angiogenesis. The present study explores the feasibility of immunotherapy of tumors by using a protein vaccine based on chicken Tie-2 as a model antigen to break the immune tolerance against Tie-2 in a cross-reaction between the xenogeneic homologous and self-Tie-2. EXPERIMENTAL DESIGN AND RESULTS: In this study, a chicken homologous Tie-2 protein vaccine (chTie-2) and a corresponding mouse Tie-2 vaccine as a control were prepared and the antitumor effect of these vaccines was tested in two tumor models (murine B16F10 melanoma and murine H22 hepatoma). Immunotherapy with chTie-2 was found effective in two tumor models. Autoantibodies against mouse Tie-2 were detected in sera of mice immunized with chTie-2 through Western blot analysis and ELISA assay. Anti-Tie-2 antibody-producing B cells were detectable by ELISPOT. Histologic examination revealed that autoantibodies were deposited on the endothelial cells of tumor tissues. Purified immunoglobulins from chTie-2-immunized mice could induce the apoptosis of human umbilical vein endothelial cells in vitro. Importantly, adoptive transfer of purified immunoglobulins led to antitumor effect in vivo; apparently, angiogenesis was significantly inhibited in these tumors. Furthermore, the antitumor activity and production of autoantibodies could be abrogated by depletion of CD4+ T lymphocytes. CONCLUSIONS: Our findings may provide a vaccine strategy for cancer therapy and show the potential utilization of interference with Tie-2 pathway.[1]References
- Immunotherapy of tumors with protein vaccine based on chicken homologous Tie-2. Luo, Y., Wen, Y.J., Ding, Z.Y., Fu, C.H., Wu, Y., Liu, J.Y., Li, Q., He, Q.M., Zhao, X., Jiang, Y., Li, J., Deng, H.X., Kang, B., Mao, Y.Q., Wei, Y.Q. Clin. Cancer Res. (2006) [Pubmed]
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