HUMAN ANTIGLIOMA MONOCLONAL-ANTIBODIES FROM PATIENTS WITH ASTROCYTIC TUMORS

The current management of malignant gliomas is unsatisfactory compared to that of other solid tumors; the expected median survival period is less than 1 year with the patient undergoing conventional surgery, ra diotherapy, and chemotherapy treatment. Immunological reagents could b e a useful adjunct. Human monoclonal antibodies derived from patients with astrocytic tumors might recognize subtle antigenic specificities that would differ from those recognized by xenogeneic (murine) systems . Five hybridomas, designated as BT27/1A2, BT27/2A3, BT32/A6, BT34/A5, and BT54/B8, were produced from the fusion of peripheral blood lympho cytes of four patients with astrocytic tumors to the human myeloma-lik e cell line TM-H2-SP2. This cell line has a 46, XX karyotype and is ne gative for hypoxanthine guanine phosphoribosyltransferase. All five hu man monoclonal antibodies produced 2.4 to 44-mu-g/ml of immunoglobulin M, had a similar but not identical pattern of reactivity against a pa nel of human tumor cell lines, and failed to react with normal human a strocytes. Labeling of four neuroectodermal tumor explant cultures by BT27/2A3 was demonstrated by flow cytometry. Karyotyping of three of t he five hybridomas demonstrated that two were pseudodiploid (2-3n) and one hypodiploid (< 2n). The monoclonality of the hybridomas was evalu ated by Southern blot analysis of J(H) gene rearrangements, revealing two types of rearrangements for each hybridoma, both consistent with m onoclonality. Preliminary antigen characterization indicated that at l east four of the five human monoclonal antibodies were directed to cel l-surface glycolipids.