Monoclonal antibodies to vascular endothelial growth factor (VEGF) and the VEGF receptor, FLT-1, inhibit the growth of C6 glioma in a mouse xenograft.
Monoclonal antibodies raised to peptide sequences of vascular endothelial growth factor (VEGF) and the VEGF receptor, FLT-1, inhibited the growth of C6 tumors growing subcutaneously in nude mice. Immunohistochemical analysis demonstrated antibody targeting of blood vessels, tumor cells, and macrophages. A control antibody demonstrated no growth inhibition or tumor uptake. An antibody to FLT- I impaired microvascular maturation and diminished the accumulation of tumor infiltrating macrophages. The antibodies demonstrated affinity for microvasculature and tumor cells in immunohistochemistry of human glioblastoma multiforme. Targeting VEGF and its receptors has potential in the treatment of tumors of the central nervous system. FLT-1 presents an attractive target due to its presence on multiple cell types.
Stefanik
D F
DF
Department of Radiation Oncology, Conemaugh Memorial Medical Center, Johnstown, PA, USA. stefanikd@msx.upmc.edu
Fellows
W K
WK
Rizkalla
L R
LR
Rizkalla
W M
WM
Stefanik
P P
PP
Deleo
A B
AB
Welch
W C
WC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy; D016228:Endothelial Growth Factors / Q000276:immunology*; D005260:Female; D005909:Glioblastoma / Q000473:pathology; D005910:Glioma / Q000098:blood supply* / Q000188:drug therapy; D006801:Humans; D007124:Immunoenzyme Techniques; D008222:Lymphokines / Q000276:immunology*; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology*; D017978:Receptors, Growth Factor / Q000276:immunology*; D040262:Receptors, Vascular Endothelial Growth Factor; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016228:Endothelial Growth Factors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor