title: Variable contribution of monoclonal antibodies to ADCC in patients with chronic lymphocytic leukemia.
abstract: Monoclonal antibodies (mAbs) are increasingly used in treatment protocols for chronic lymphocytic leukemia (CLL). Here we determined (i) the extent of antibody-dependent cellular cytotoxicity (ADCC) of four different mAbs against primary CLL cells, (ii) whether ADCC correlates with antigen density on CLL cells, and (iii) whether allogeneic natural killer (NK) cells display superior ADCC than autologous. Effector cells for ADCC were (i) NK-92 cells not expressing FcR, (ii) NK-92 cells transfected with a high-affinity Fc receptor, (iii) autologous NK cells from patients with CLL, (iv) allogeneic NK cells. Results suggest that ADCC contributes to killing of CLL cells by anti-CD20 antibodies (rituximab and veltuzumab), whereas mAbs against CD22 (epratuzumab) and CD23 (lumiliximab) showed minimal ADCC. The magnitude of anti-CD20 mediated ADCC did not correlate with antigen density of CD20. ADCC was not influenced by the FcR genotype expressed by autologous NK cells. Allogeneic NK cells were superior to autologous NK cells in killing primary CLL cells.
authors: Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
authors: James
authors: J
authors: Weitzman
authors: Monica
authors: M
authors: Betancur
authors: Laurent
authors: L
authors: Boissel
authors: Arthur P
authors: AP
authors: Rabinowitz
authors: Andreas
authors: A
authors: Klein
authors: Hans
authors: H
authors: Klingemann
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology*; D000074301:CD52 Antigen; D045744:Cell Line, Tumor / Q000276:immunology; D005838:Genotype; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D000069283:Rituximab; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D018951:Antigens, CD20; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C497867:CD22 protein, human; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2; C448700:epratuzumab; D000069283:Rituximab; C509683:lumiliximab; C493846:veltuzumab