[Specific anti-glioma angiogenesis immune response induced by attenuated Salmonella typhimurium vaccine expressing vascular endothelial growth factor receptor-2].
OBJECTIVE
Vascular endothelial growth factor (VEGF) and its receptor (VEGFR-2) play important roles in tumor angiogenesis. This study was to investigate anti-vasculature and anti-glioma effects of attenuated Salmonella typhimurium vaccine expressing VEGFR2 gene.


METHODS
Plasmid pcDNA3.1-VEGFR2 was constructed, and electrotransfected into attenuated Salmonella typhimurium strain SL7207. C57BL/6J mice were immunized with gastrogavage of cDNA vaccine encoding VEGFR2 (vaccine group). C57BL/6J mice received gastrogavage of pcDNA3.1 or NaHCO3 were used as controls. Serum level of specific anti-VEGFR2-IgG antibody was detected by ELISA. Cytotoxic T lymphocytes (CTLs) activity was measured by MTT assay. Mouse models of intracranial Gl261 glioblastoma were treated with gastrogavage of attenuated Salmonella typhimurium expressing VEGFR2 gene. Tumor diameter was measuredu microvessel density (MVD) was detected by immunohistochemistryu tumor cell apoptosis was detected by TUNEL.


RESULTS
All mice immunized with the vaccine developed high levels of anti-VEGFR2-IgG antibody, and showed strong CTLs activities against VEGFR2. The vaccine substantially inhibited glioblastoma growth. MVD was significantly lower in vaccine group than in pcDNA3.1 group, and NaHCO3 group (8.8+/-1.9 vs. 27.2+/-4.5, and 26.5+/-5.8, P < 0.01)u while apoptotic cell count per visual field was significantly higher in vaccine group than in the rest 2 groups (23.4+/-4.7 vs. 3.1+/-1.0, and 4.4+/-1.2, P < 0.01).


CONCLUSIONS
Attenuated Salmonella typhimurium vaccine expressing VEGFR2 gene can break immunologic tolerance against self-VEGFR2 antigen, and specifically kill glioblastoma vascular endothelial cells by inducing specific anti-VEGFR2 immunoreaction.
Feng
Ke-Ke
KK
Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, P.R.China. fengke1976@sohu.com
Zhao
Hong-Yang
HY
Qiu
Hui
H
Chen
Jian
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D005910:Glioma / Q000473:pathology*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010957:Plasmids; D011897:Random Allocation; D022562:Salmonella Vaccines / Q000276:immunology / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
D007074:Immunoglobulin G; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D040301:Vascular Endothelial Growth Factor Receptor-2