An immunotoxin prepared with blocked ricin: a natural plant toxin adapted for therapeutic use.

摘要: Ricin, the cytotoxic protein isolated from castor beans, is composed of two subunits, A-chain and B-chain. Ricin intoxicates cells by binding through its B-chain to galactose-terminated oligosaccharides found on surface all eukaryotic then transferring cytosol where it disrupts synthesis inactivating ribosomes. In addition binding, plays an important, but not yet understood, role in translocation a cellular membrane cytosol. Blocking galactose-binding sites native ricin chemical modification with affinity ligands created altered toxin, called blocked ricin, that has at least 3500-fold lower more than 1000-fold less for Namalwa (a Burkitt's lymphoma line) maintained function catalytic activity A-chain. Conjugation monoclonal antibodies bind cell antigens creates new cytotoxins approach potency ricin. These incorporate three essential functions natural toxins, i.e. , cells, transport membrane, inactivation process; they possess defined target specificity. Such potent immunotoxins may play important therapeutic cancer treatment. Clinical trials anti-CD19-blocked anti-CD33-blocked conjugate against B-cell cancers acute myeloblastic leukemia have begun.