Immunotherapy of tumors with vaccine based on quail homologous vascular endothelial growth factor receptor-2

Ji Yan Liu, Yu Quan Wei, Li Yang, Xia Zhao, Ling Tian, Jian Mei Hou, Ting Niu, Fen Liu, Yu Jiang, Bing Hu, Yang Wu, Jing Mei Su, Yan Yan Lou, Qiu Ming He, Yan Jun Wen, Jin Liang Yang, Bing Kan, Yong Qiu Mao, Feng Luo, Feng Peng

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120 Scopus citations

Abstract

The breaking of immune tolerance of "self-antigens" associated with angiogenesis is an attractive approach to cancer therapy by active immunity. We used vascular endothelial growth factor receptor-2 (VEGFR-2) as a model antigen to explore the feasibility of the immunotherapy with a vaccine based on a xenogeneic homologous protein. To test this concept, we prepared a quail homologous VEGFR-2 protein vaccine (qVEGFR) based on quail VEGFR-2. At the same time, a protein vaccine based on the corresponding ligand-binding domain of mouse self-VEGFR-2 (mVEGFR) was also prepared and used as a control. We found that immunotherapy with qVEGFR was effective at protective and therapeutic antitumor immunity in several solid and hematopoietic tumor models in mice. Autoantibodies against mouse VEGFR-2 (Flk-1) were identified by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Anti-VEGFR antibody-producing B cells were detectable by ELISPOT. Endothelial deposition of immunoglobulins developed within tumor. VEGF-mediated endothelial cell proliferation was inhibited in vitro by immunoglobulins from qVEGFR-immunized mice. Antitumor activity was caused by the adoptive transfer of the purified immunoglobulins. Antitumor activity and production of autoantibodies against Flk-1 could be abrogated by the depletion of CD4+ T lymphocytes. Angiogenesis was apparently inhibited within the tumors, and the vascularization of alginate beads was also reduced. No marked toxicity was found in the immunized mice. The observations may provide a vaccine strategy for cancer therapy through the induction of autoimmunity against the growth factor receptor associated with angiogenesis in a cross-reaction with single xenogeneic homologous protein.

Original languageEnglish (US)
Pages (from-to)1815-1823
Number of pages9
JournalBlood
Volume102
Issue number5
DOIs
StatePublished - Sep 1 2003

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Liu, J. Y., Wei, Y. Q., Yang, L., Zhao, X., Tian, L., Hou, J. M., Niu, T., Liu, F., Jiang, Y., Hu, B., Wu, Y., Su, J. M., Lou, Y. Y., He, Q. M., Wen, Y. J., Yang, J. L., Kan, B., Mao, Y. Q., Luo, F., & Peng, F. (2003). Immunotherapy of tumors with vaccine based on quail homologous vascular endothelial growth factor receptor-2. Blood, 102(5), 1815-1823. https://doi.org/10.1182/blood-2002-12-3772