Our studies have confirmed the presence of large concentrations of various
intermediate filament proteins (IFPs) in
glioma tissue compared to normal brain. This avenue of research was extended to assess the anti-proliferative activity of anti-intermediate filament
protein monoclonal antibodies (anti-IFP mAbs) against human
glioma cells. In this study, anti-proliferative activity of
glial fibrillary acidic protein monoclonal antibodies (anti-GFAP mAbs) has been tested in vitro, using
glioma cell lines prepared and established from freshly resected
brain tumors. One
anaplastic astrocytoma (AA), two
glioblastoma multiforme (GB1 and GB2) cell lines and three anti-GFAP mAbs (B12C4, B12B4 and B6C6, all
IgG1, kappa) were used. Immunofluorescence study indicated the ability of anti-GFAP mAbs to recognize the cell surface of
glioma cells and the inhibition study showed that mAb B12B4 inhibited the proliferation of GB1 (96%), GB2 (85%) and AA (93%) at a concentration of 3.2 x 10(-10) M. mAb B12C4 inhibited the proliferation of GB1 (95%), GB2 (86%) and AA (94%) at a concentration of 3.26 x 10(-10) M and mAb B6C6 inhibited the proliferation of GB1 (75%), GB2 (75%) and AA (91%) at a concentration of 2.074 x 10(-10) M.
Thymidine release assay demonstrated the cytolytic activities of anti-GFAP mAbs towards these
glioma cell lines, and this observation was confirmed by
dye exclusion, which indicated the lysis of
glioma cells after anti-GFAP mAbs treatment. Anti-GFAP mAbs had little effect (< or = 20%) on normal human lymphocyte, liver and intestine cell lines. These results look promising for radioimaging and
immunotherapy of human
gliomas.