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.

Acidic and basic fibroblast growth factors are present in glioblastoma multiforme.

Immunohistochemistry was performed on paraffin sections from human glioblastoma multiforme and normal brain tissue. Acidic fibroblast growth factor (FGF) was abundantly present in astrocytes from all glioblastomas studied. Basic FGF was found in the matrix surrounding proliferating blood vessels in most of the glioblastomas. In contrast, astrocytes from normal brain did not contain acidic FGF, and perivascular matrix staining was not demonstrated for basic FGF in the normal brain. Both growth factors could be demonstrated in neurons, Purkinje cells, capillary endothelium, and arterial walls in the normal brain. This study implicates both growth factors in the pathogenesis of malignant glioma. Both may be significant mediators of angiogenesis in glioblastoma.