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 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.
Abaza
M S
MS
Department of Biochemistry, Baylor College of Medicine, Houston, Texas, USA.
Narayan
R K
RK
Atassi
M Z
MZ
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology*; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D005904:Glial Fibrillary Acidic Protein; D014316:Tritium; D013936:Thymidine