Antibody-ricin conjugates: a method of linkage which blocks the galactose binding site of ricin.
Conjugates of the monoclonal antibody anti-Thy 1:1 (OX7) and ricin have been constructed, using a thioether bond, such that the ricin no longer can bind Sepharose or asialofetuin. These conjugates were found to be very toxic to Thy 1:1 expressing AKR-A cells whereas they showed little toxicity to Thy 1:2 expressing EL4 cells. By comparison, OX7-ricin conjugates which retained galactose-binding capability were still highly toxic to EL4 cells and this toxicity was antagonized by lactose. A second conjugate made from the W3/25 monoclonal antibody was constructed. The W3/25-ricin conjugate which had lost Sepharose-binding capacity was toxic to W3/25 antigen-expressing rat T-leukaemia cells. This is in sharp contrast to the disulphide linked W3/25-ricin A-chain conjugate which is totally inactive, suggesting that the role of the B-chain in membrane transport of the A-chain into the cytosol is independent of galactose recognition.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D001667:Binding, Competitive; D002850:Chromatography, Gel; D005690:Galactose / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008223:Lymphoma / Q000276:immunology; D051381:Rats; D011975:Receptors, Mitogen / Q000378:metabolism*; D012276:Ricin / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011975:Receptors, Mitogen; D012276:Ricin; D005690:Galactose