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

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...

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Veröffentlicht in:Blood 2003-09, Vol.102 (5), p.1815-1823
Hauptverfasser: Liu, Ji-yan, Wei, Yu-quan, Yang, Li, Zhao, Xia, Tian, Ling, Hou, Jian-mei, Niu, Ting, Liu, Fen, Jiang, Yu, Hu, Bing, Wu, Yang, Su, Jing-mei, Lou, Yan-yan, He, Qiu-ming, Wen, Yan-jun, Yang, Jin-liang, Kan, Bing, Mao, Yong-qiu, Luo, Feng, Peng, Feng
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Sprache:eng
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Zusammenfassung: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2002-12-3772