Delivery of ricin and abrin A-chains to human carcinoma cells in culture following covalent linkage to monoclonal antibody LICR-LOND-Fib 75.
With the object of generating specific cytotoxic agents, we have prepared covalent conjugates of the A-chains of ricin and of abrin with monoclonal antibody LICR-LOND-Fib 75 and investigated their toxicity toward a human tumor cell line in culture. Both conjugates proved to be potent cytotoxins toward cells carrying the appropriate antigen. The agent containing abrin A-chain was toxic at a significantly lower concentration and exerted its maximum effect more rapidly than the one containing ricin A-chain. Inclusion of chloroquine in the incubation medium significantly enhanced the toxic action of both conjugates without loss of immunospecificity. Because of the widespread occurrence on human tumor cell lines of the antigen recognized by Fib 75, these conjugates, particularly the one containing abrin A-chain, may find application in freeing human bone marrow ex vivo of infiltrated tumor cells prior to reinfusion as an autograft.
D000036:Abrin / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000276:immunology / Q000473:pathology*; D010940:Plant Proteins / Q000008:administration & dosage*; D011817:Rabbits; D012276:Ricin / Q000008:administration & dosage*
D000911:Antibodies, Monoclonal; D010940:Plant Proteins; D000036:Abrin; D002738:Chloroquine; D012276:Ricin