THE SPECIFIC CYTOTOXICITY OF IMMUNOCONJUGATES CONTAINING BLOCKED RICIN IS DEPENDENT ON THE RESIDUAL BINDING-CAPACITY OF BLOCKED RICIN - EVIDENCE THAT THE MEMBRANE-BINDING AND A-CHAIN TRANSLOCATION ACTIVITIES OF RICIN CANNOT BE SEPARATED

Recently we have developed blocked ricin, a derivative of native ricin in which the galactose-binding sites of the B-chain are blocked by covalent modification with affinity ligands. This modification impedes the binding function of the B-chain, while sparing its ability to facilitate the entry of the toxic subunit of ricin, the A-chain, into the cytoplasm. Immunotoxins prepared with blocked ricin approach the cytotoxic potency of native ricin with antibody-dependent specificity. Here we report that the high cytotoxic potency of these immunoconjugates, which is attributed to the preserved translocation function of the ricin B-chain, is dependent on the minimal residual lectin activity of blocked ricin. Our findings support the notion that two functions of ricin, membrane binding and translocation, cannot be separated. © 1992.