The Use of Ricin a Chain-Containing Immunotoxins to Kill Neoplastic B Cells
Paul Ehrlich first discussed the potential use of antibodies as carriers of pharmacologic agents. During the last 10 years there have been many attempts to apply this concept to the elimination of neoplastic and other target cells using antibodies coupled to toxic agents. A cell-binding antibody conjugated to a plant or bacterial toxin has been termed an “immunotoxin”. One such toxin, ricin, like most toxic proteins produced by bacteria and plants, has a toxic polypeptide (A chain) attached to a cell binding polypeptide (B chain) (Olsnes and Pihl, 1973). The B chain is a lectin that binds to galactose-containing glycoproteins or glycolipids on the cell surface. By mechanisms that are not yet well understood, the A chain of the cell-bound ricin gains access to the cell cytoplasm presumably by receptor-mediated endocytosis and penetration of the membrane of the endocytic vesicle (Olsnes and Pihl, in press). There is evidence that the B chain can also facilitate the translocation of the A chain through the membrane of the endocytic vesicle, possibly by forming a pore (Jansen, et al., 1982; Neville and Youle, 1982; Thorpe and Ross, 1982; Houston, 1982). In the cytoplasm, the A chain of ricin inhibits protein synthesis by enzymatically inactivating the EF-2 binding portion of the 60S ribosomal subunit.
KeywordsChronic Lymphocytic Leukemia Endocytic Vesicle Daudi Cell Total Lymphoid Irradiation Prolymphocytic Leukemia
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