Inhibition of tumor growth with a vaccine based on xenogeneic homologous fibroblast growth factor receptor-1 in mice

Qiu ming He, Yu quan Wei, Ling Tian, Xia Zhao, Jing mei Su, Li Yang, You Lu, Bin Kan, Yan yan Lou, Mei juan Huang, Fei Xiao, Ji yan Liu, Bing Hu, Feng Luo, Yu Jiang, Yan jun Wen, Hong xin Deng, Jiong Li, Tin Niu, Jin liang Yang

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Angiogenesis is important for the growth of solid tumors. The breaking of the immune tolerance against the molecule associated with angiogenesis should be a useful approach for cancer therapy. However, the immunity to self-molecules is difficult to elicit by a vaccine based on autologous or syngeneic molecules due to immune tolerance. Basic fibroblast growth factor (bFGF) is a specific and potent angiogenic factor implicated in tumor growth. The biological activity of bFGF is mediated through interaction with its high-affinity receptor, fibroblast growth factor receptor-1 (FGFR-1). In this study, we selected Xenopus FGFR-1 as a model antigen by the breaking of immune tolerance to explore the feasibility of cancer therapy in murine tumor models. We show here that vaccination with Xenopus FGFR-1 (pxFR1) is effective at antitumor immunity in three murine models. FGFR-1-specific autoantibodies in sera of pxFR1-immunized mice could be found in Western blotting analysis. The purified immunoglobulins were effective at the inhibition of endothelial cell proliferation in vitro and at the antitumor activity in vivo. The antitumor activity and production of FGFR-1-specific autoantibodies could be abrogated by depletion of CD4+ T lymphocytes. Histological examination revealed that the autoantibody was deposited on the endothelial cells within tumor tissues from pxFR1-immunized mice, and intratumoral angiogenesis was significantly suppressed. Furthermore, the inhibition of angiogenesis could also be found in alginate-encapsulate tumor cell assay. These observations may provide a new vaccine strategy for cancer therapy through the induction of autoimmunity against FGFR-1 associated with angiogenesis in a cross-reaction.

Original languageEnglish (US)
Pages (from-to)21831-21836
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number24
DOIs
StatePublished - Jun 13 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    He, Q. M., Wei, Y. Q., Tian, L., Zhao, X., Su, J. M., Yang, L., Lu, Y., Kan, B., Lou, Y. Y., Huang, M. J., Xiao, F., Liu, J. Y., Hu, B., Luo, F., Jiang, Y., Wen, Y. J., Deng, H. X., Li, J., Niu, T., & Yang, J. L. (2003). Inhibition of tumor growth with a vaccine based on xenogeneic homologous fibroblast growth factor receptor-1 in mice. Journal of Biological Chemistry, 278(24), 21831-21836. https://doi.org/10.1074/jbc.M300880200