title: GA101 induces NK-cell activation and antibody-dependent cellular cytotoxicity more effectively than rituximab when complement is present.
abstract: Both complement and antibody-dependent cellular cytotoxicity (ADCC) contribute to the clinical efficacy of anti-CD20 monoclonal antibody (mAb) therapy. Paradoxically, the C3b component of complement can block interaction between mAb and natural killer (NK) cells. The present study compared the effect of complement on the ability of two anti-CD20 mAbs, rituximab and GA101, to activate NK cells and mediate ADCC. Complement blocked adherence of NK cells to rituximab, but had little effect on NK binding to GA101. Target cells coated with rituximab or GA101 were able to activate NK cells in the absence of serum. Complement in serum blocked NK activation induced by rituximab, but not GA101. Complement blocked rituximab-induced NK-cell mediated ADCC, but not GA101-induced ADCC. These results demonstrate that the decreased ability of GA101 to fix complement relative to rituximab results in an enhanced ability of GA101 to bind to NK cells, activate NK cells and induce ADCC when serum is present.
authors: University of Iowa Graduate Program in Immunology.
authors: Delila J
authors: DJ
authors: Kern
authors: Britnie R
authors: BR
authors: James
authors: Sue
authors: S
authors: Blackwell
authors: Christian
authors: C
authors: Gassner
authors: Christian
authors: C
authors: Klein
authors: George J
authors: GJ
authors: Weiner
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000378:metabolism / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000378:metabolism / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D002460:Cell Line; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism; D003182:Complement C5 / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D011485:Protein Binding / Q000276:immunology; D000069283:Rituximab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D003182:Complement C5; D000069283:Rituximab; D015922:Complement C1q; D003165:Complement System Proteins; C543332:obinutuzumab