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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-8-21
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
102
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1815-23
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12750177-Animals, pubmed-meshheading:12750177-Antigens, Heterophile, pubmed-meshheading:12750177-Autoantibodies, pubmed-meshheading:12750177-Cancer Vaccines, pubmed-meshheading:12750177-Carcinoma, Lewis Lung, pubmed-meshheading:12750177-Colonic Neoplasms, pubmed-meshheading:12750177-Fibrosarcoma, pubmed-meshheading:12750177-Immunotherapy, pubmed-meshheading:12750177-Lung Neoplasms, pubmed-meshheading:12750177-Lymphoma, pubmed-meshheading:12750177-Mice, pubmed-meshheading:12750177-Mice, Inbred BALB C, pubmed-meshheading:12750177-Mice, Inbred C57BL, pubmed-meshheading:12750177-Neoplasm Transplantation, pubmed-meshheading:12750177-Neovascularization, Pathologic, pubmed-meshheading:12750177-Plasmacytoma, pubmed-meshheading:12750177-Quail, pubmed-meshheading:12750177-T-Lymphocyte Subsets, pubmed-meshheading:12750177-Vascular Endothelial Growth Factor Receptor-2
pubmed:year
2003
pubmed:articleTitle
Immunotherapy of tumors with vaccine based on quail homologous vascular endothelial growth factor receptor-2.
pubmed:affiliation
Key Laboratory of Biotherapy of Human Diseases and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Guo Xue Xiang, No. 37, Chengdu, Sichuan, 610041, The People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't