A carcinoembryonic antigen-directed immunotoxin built by linking a monoclonal antibody to a hemolytic toxin

✍ Scribed by A. D. Avila; C. De Mateo Acosta; A. Lage

• Book ID: 102868602
• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: French
• Weight: 502 KB
• Volume: 43
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910430533

✦ Synopsis

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. lmmunotoxins based on membraneactive, 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 a 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.