38.13: a monoclonal antibody directed against a Burkitt's lymphoma-associated antigen and its use as carrier for toxins.
We have previously described a monoclonal antibody, referred to as 38.13, reacting with most Burkitt's lymphoma (BL) derived lines, both with and without Epstein-Barr virus (EBV), but not reacting with EBV-positive lymphoblastoid cell lines (Wiels et al., 1981, 1982). The antibody reacted with 41 BL lines out of 57 tested. The target antigen, BLA, was shown to be a neutral glycolipid, identified as globotriaosylceramide (Gal alpha 1----4Gal beta 1----4 Glc beta 1----1 ceramide) (Nudelman et al., 1983). This substance is known as the blood group antigen Pk, a normal intermediate in the P-substance synthesis. The 38.13 antibody was covalently linked to either ricin-A chain or gelonin toxin, and its anti-BL specificity remained unaffected. Both immunotoxins were highly cytotoxic for cultured BL cells. The kinetics of the toxic effects of the immunotoxins on these cells appeared to be strikingly fast, since 50% protein synthesis inhibition was achieved after two hours' incubation. These kinetics are similar to those obtained with entire ricin, and clearly different from those observed when using immunotoxins directed against protein antigens (16-30 h). When longer incubation times are used, killing of apparently irrelevant targets was reproducibly observed. These data suggest the presence of a low number of antigenic sites on non-Burkitt cells. The detection of a low number of antigenic sites by immunotoxins directed towards such glycolipid antigens might not be a disadvantage, but might rather permit efficient and rapid killing of a wide variety of tumour cells.
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D010940:Plant Proteins / Q000627:therapeutic use; D054789:Ribosome Inactivating Proteins, Type 1; D012276:Ricin / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum; D012276:Ricin