Synergy between immunotoxins prepared with native ricin A chains and chemically-modified ricin B chains.
Ricin B chains treated with chloramine-T in the presence or absence of NaI show a 100-fold to 200-fold reduction in their ability to bind to the galactose-containing protein asialofetuin. Such treated B chains do not form covalently associated homodimers with treated B chains or heterodimers with native ricin A chains. Furthermore, they cannot enhance the toxicity of a ricin A chain-containing rabbit anti-human immunoglobulin (RAHIg-A) for Daudi cells. However, when such B chains are coupled to goat anti-rabbit Ig (GARIg), they potentiate the killing of RAHIg-A-treated Daudi cells only slightly less effectively than GARIg coupled to native B chains. Furthermore, if GARIg-B chain conjugates are treated with chloramine-T after coupling, they fail to bind to asialofetuin but enhance the killing of Daudi cells treated with RAHIg-A. These results demonstrate that the ability of ricin B chains to bind to galactose and to enhance the toxicity of ricin A chains (in the form of an antibody-A chain) can be operationally separated. Thus, the two functions of the B chain may reside on separate domains of the molecule.
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D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000502:physiology; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D000970:Antineoplastic Agents / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D001212:Asialoglycoproteins; D001666:Binding Sites, Antibody / Q000187:drug effects; D002460:Cell Line; D002700:Chloramines / Q000494:pharmacology; D004357:Drug Synergism; D060748:Fetuins; D006041:Goats; D006801:Humans; D011108:Polymers / Q000138:chemical synthesis; D011817:Rabbits; D012276:Ricin / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D012974:Sodium Iodide / Q000494:pharmacology; D014105:Tosyl Compounds; D000509:alpha-Fetoproteins / Q000378:metabolism
D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic; D000970:Antineoplastic Agents; D001212:Asialoglycoproteins; D002700:Chloramines; D060748:Fetuins; D011108:Polymers; D014105:Tosyl Compounds; D000509:alpha-Fetoproteins; C017029:asialofetuin; C016300:chloramine-T; D012276:Ricin; D012974:Sodium Iodide