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

Yu Quan Wei, Mei Juan Huang, Li Yang, Xia Zhao, Ling Tian, You Lu, Jing Mei Shu, Chong Jiu Lu, Ting Niu, Bin Kang, Yun Qiu Mao, Fen Liu, Yan Jun Wen, Shong Lei, Feng Luo, Li Qun Zhou, Feng Peng, Yu Jiang, Ji Yan Liu, Hao ZhouQing Ru Wang, Qiu Ming He, Fei Xiao, Yan Yan Lou, Xing Jiang Xie, Qiu Li, Yang Wu, Zhen Yu Ding, Bin Hu, Min Hu, Wei Zhang

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Abstract

Overcoming immune tolerance of the growth factors associated with tumor growth should be a useful approach to cancer therapy by active immunity. We used vascular endothelial growth factor (VEGF) as a model antigen to explore the feasibility of the immunogene tumor therapy with a vaccine based on a single xenogeneic homologous gene, targeting the growth factors associated with angiogenesis. To test this concept, we constructed a plasmid DNA encoding Xenopus homologous VEGF (XVEGF-p) and control vectors. We found that immunogene tumor therapy with a vaccine based on XVEGF was effective at both protective and therapeutic antitumor immunity in several tumor models in mice. VEGF-specific autoantibodies in sera of mice immunized with XVEGF-p could be found in Western blotting analysis and ELISA assay. The purified immunoglobulins were effective at the inhibition of VEGF-mediated endothelial cell proliferation in vitro, and at antitumor activity and the inhibition of angiogenesis by adoptive transfer in vivo. The elevation of VEGF in the sera of the tumor-bearing mice could be abrogated with XVEGF-p immunization. The antitumor activity and production of VEGF-specific autoantibodies, significantly elevated IgG1 and IgG2b, could be abrogated by the depletion of CD4+ T lymphocytes. The observations may provide a vaccine strategy for cancer therapy through the induction of autoimmunity against the growth factors associated with tumor growth in a cross reaction with single xenogeneic homologous gene and may be of importance in the further exploration of the applications of other xenogeneic homologous genes identified in human and other animal genome sequence projects in cancer therapy.

Original languageEnglish (US)
Pages (from-to)11545-11550
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number20
DOIs
StatePublished - Sep 25 2001

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Wei, Y. Q., Huang, M. J., Yang, L., Zhao, X., Tian, L., Lu, Y., Shu, J. M., Lu, C. J., Niu, T., Kang, B., Mao, Y. Q., Liu, F., Wen, Y. J., Lei, S., Luo, F., Zhou, L. Q., Peng, F., Jiang, Y., Liu, J. Y., ... Zhang, W. (2001). Immunogene therapy of tumors with vaccine based on Xenopus homologous vascular endothelial growth factor as a model antigen. Proceedings of the National Academy of Sciences of the United States of America, 98(20), 11545-11550. https://doi.org/10.1073/pnas.191112198