IN-VIVO INHIBITION OF ANGIOGENESIS AND GROWTH OF THE HUMAN U-87 MALIGNANT GLIAL TUMOR BY TREATMENT WITH AN ANTIBODY AGAINST BASIC FIBROBLAST GROWTH-FACTOR

The effectiveness of in vivo suppression of neovascularization and gro wth of malignant glial tumors by in situ administration of an antibody directed against basic fibroblast growth factor (bFGF), a strong mito gen for cells of mesodermal origin, was tested. One hundred fifty cong enitally athymic nude rats (Han rnu/rnu) were implanted intracerebrall y with U-87MG tumor cells, known constitutive producers of bFGF. The a nimals were randomly assigned to six groups of 25 animals each. Animal s were treated by in situ application of saline (Group F), control ant ibody (Group D), or polyclonal anti-bFGF antibody (Group B). In additi onal groups a putative effect on tumor growth caused by the treatment application device itself (between growth control Groups A and E), and the effect of heat-inactivated tumor cells (negative control Group C) were tested. After 3 weeks of treatment, tumor progression and degree of neovascularization were morphometrically recorded. In the untreate d Groups A and E massive tumor growth was recorded, consisting of 19.9 % +/- 0.4% and 27.1% +/- 0.5%, respectively, of the total brain cross- sectional area. In Group C, no tumor growth occurred. In control Group s D and F tumor progression consisted of 18.6% +/- 0.4% and 18.5% +/- 0.4%, respectively, of the total brain cross-sectional area; whereas i n the anti-bFGF treated Group B, significantly smaller tumor masses me asuring 7.2% +/- 0.1% were recorded. New blood vessels were located bo th peritumorally and intratumorally and defined as numerical density a nd area fraction (number/area and area/area). Significantly more new b lood vessels were found in Groups A, D, E, and F, ranging from 41,380/ mm(2) +/- 464/mm(2) to 53,442/mm(2) +/- 150/mm(2) peritumorally and 51 ,846/mm(2) +/- 495/mm(2) to 64,660/mm(2) +/- 183/mm(2) intratumorally than in the anti-bFGF treated Group B, which numbered 8220/mm(2) +/- 2 25/mm(2) peritumorally and 16,554/mm(2) +/- 236/mm(2) intratumorally. The authors conclude that treatment with anti-bFGF antibody is effecti ve in inhibiting tumor-induced angiogenesis and correlated tumor progr ession. However, owing to the character of the experimental system use d, one cannot exclude the possibility that application of the specific anti-bFGF antibody also counteracts device-induced neovascularization . The authors suggest that combined surgical excision and adjuvant imm unotherapy of tumors such as glioblastoma and other malignant brain tu mors that express bFGF might prevent tumor recurrence.