IN-VITRO EFFICACY OF ANTI-GLIAL FIBRILLARY ACIDIC PROTEIN MONOCLONAL-ANTIBODIES AGAINST HUMAN-MALIGNANT GLIOMA CELL-LINES

Our studies have confirmed the presence of large concentrations of var ious intermediate filament proteins (IFPs) in glioma tissue compared t o normal brain. This avenue of research was extended to assess the ant i-proliferative activity of anti-intermediate filament protein monoclo nal antibodies (anti-IFP mAbs) against human glioma cells. In this stu dy, anti-proliferative activity of glial fibrillary acidic protein mon oclonal antibodies (anti-GFAP mAbs) has been tested in vitro, using gl ioma cell lines prepared and established from freshly resected brain t umors. One anaplastic astrocytoma (AA), two glioblastoma multiforme (G B(1) and GB(2)) cell lines and three anti-GFAP mAbs (B12C4, B12B4 and B6C6, all IgG(1), 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 pr oliferation of GB(1) (96%), GB(2) (85%) and AA (93%) at a concentratio n of 3.2 x 10(-10) M. mAb B12C4 inhibited the proliferation of GB(1) ( 95%), GB(2) (86%) and AA (94%) at a concentration of 3.26 x 10(-10) M and mAb B6C6 inhibited the proliferation of GB(1) (75%), GB(2) (75%) a nd 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 ex clusion, which indicated the lysis of glioma cells after anti-GFAP mAb s treatment. Anti-GFAP mAbs had little effect (less than or equal to 2 0%) on normal human lymphocyte, liver and intestine cell lines. These results look promising for radioimaging and immunotherapy of human gli omas.