A carcinoembryonic antigen-directed immunotoxin built by linking a monoclonal antibody to a hemolytic toxin.
Hybrid molecules prepared by linking toxins to monoclonal antibodies (MAbs) are cytotoxic to cells bearing the target antigen. The toxin most widely used has been the plant toxin ricin as the toxic component, which inhibits protein synthesis at the ribosome level. Immunotoxins based on membrane-active, hemolytic toxins can be a useful alternative when directed towards antigens which do not mediate internalization, as is the case for most carcinoma antigens. We present an alternative for toxic components using a hemolytic toxin acting at the membrane level, due to its phospholipase activity. The hemolytic toxin (HT), isolated from the sea anemone Stoichactis helianthus, has been conjugated to a MAb directed against carcinoembryonic antigen (CEA), by means of an artificial disulphide bridge. The hybrid alpha CEA-HT exhibits no hemolytic activity unless it is reduced. It is toxic for cells (MDA-MB-134) expressing CEA and not toxic for cells (MDA-MB-231) not bearing CEA. An excess of free antibody reverses toxicity.
Avila
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Instituto Nacional de Oncología y Radiobiología, MINSAP, Ciudad de la Habana, Cuba.
Mateo de Acosta
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Lage
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D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006460:Hemolysin Proteins / Q000494:pharmacology*; D006801:Humans; D000922:Immunotoxins / Q000302:isolation & purification / Q000494:pharmacology*; D008970:Molecular Weight; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D006460:Hemolysin Proteins; D000922:Immunotoxins