Immunotoxins: hybrid molecules of monoclonal antibodies and a toxin subunit specifically kill tumour cells

• Published in: Nature (London) 1981-03, Vol.290 (5802), p.145-146
• Main Authors: Blythman, Hildur E, Casellas, Pierre, Gros, Olivier, Gros, Pierre, Jansen, Franz K, Paolucci, Francis, Pau, Bernard, Vidal, Hubert
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Neoplasm - administration & dosage; Antibody Specificity; Antineoplastic Agents - administration & dosage; Cells, Cultured; Clone Cells; Humanities and Social Sciences; Immunoglobulin M - administration & dosage; letter; Leukemia, Experimental - drug therapy; Mice; Mice, Inbred BALB C; multidisciplinary; Neoplasm Transplantation; Ricin - administration & dosage; Science; Science (multidisciplinary); Toxins, Biological - metabolism
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/290145a0

Several attempts to attack tumours in experimental systems have been made using conjugates of chemotherapeutic agents or potent toxins with antibodies (immunotoxins) 1–8 . In vitro studies have been highly successful, showing target specificity of a high order in some cases 6–8 . However, so far, such conjugates have been inadequate in vivo , probably for two main reasons. First, conventional heteroclonal antibodies are perhaps inappropriate, because purification by biochemical methods leaves a large amount of non-antibody γ-globulins. The use of monoclonal antibodies may overcome this problem. Second, when whole toxins have been conjugated to antibodies there has been a strong residual nonspecific cytotoxicity due to the binding capacity of a subunit, the B-piece of the toxin. (Diphtheria toxin or ricin consist of two polypeptide subunits. The A-piece is responsible for inhibition of protein synthesis on ribosomes, and the B-piece binds to galactose residues on the cell membrane and facilitates the transmembrane passage of the A-piece.) In the present work the problem of nonspecific binding by the B-piece has been circumvented by using the A-piece only as the toxin component of immunotoxins; these immunotoxins are active both in vitro and in vivo .