Rituximab infusion induces NK activation in lymphoma patients with the high-affinity CD16 polymorphism
- 22 September 2011
- journal article
- Published by American Society of Hematology in Blood
- Vol. 118 (12) , 3347-3349
- https://doi.org/10.1182/blood-2011-05-351411
Abstract
Natural killer (NK) cell–mediated antibody-dependent cellular cytotoxicity involving FcγRIIIa (CD16) likely contributes to the clinical efficacy of rituximab. To assess the in vivo effects of CD16 polymorphisms on rituximab-induced NK activation, blood was evaluated before and 4 hours after initiation of the initial dose of rituximab in 21 lymphoma subjects. Rituximab induced NK activation and a drop in circulating NK-cell percentage in subjects with the high-affinity [158(VF/VV)] but not the low-affinity [158(FF)] CD16 polymorphism. There was no correlation between NK-cell activation or NK-cell percentage and polymorphisms in CD32A, C1q, or CH50. We conclude that NK activation occurs within 4 hours of rituximab infusion in subjects with the high-affinity CD16 polymorphism but not those with the low-affinity CD16 polymorphism. This finding may help explain the superior clinical outcome seen in the subset of high-affinity CD16 polymorphism lymphoma patients treated with single-agent rituximab.Keywords
This publication has 21 references indexed in Scilit:
- Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell–mediated B-cell cytotoxicityBlood, 2010
- Rituximab: Therapeutic Benefit! Vitamin R?Seminars in Hematology, 2010
- Depletion of the C3 component of complement enhances the ability of rituximab-coated target cells to activate human NK cells and improves the efficacy of monoclonal antibody therapy in an in vivo modelBlood, 2009
- Measuring Granulocyte and Monocyte Accumulation at Malignant Lymphoma SitesJournal of Clinical Oncology, 2009
- A Polymorphism in the Complement ComponentC1qACorrelates with Prolonged Response Following Rituximab Therapy of Follicular LymphomaClinical Cancer Research, 2008
- NK-cell activation and antibody-dependent cellular cytotoxicity induced by rituximab-coated target cells is inhibited by the C3b component of complementBlood, 2008
- Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower concentrations and more effectively than rituximabBlood, 2006
- Polymorphisms in FcγRIIIA (CD16) Receptor Expression Are Associated With Clinical Response to Rituximab in Waldenström’s MacroglobulinemiaJournal of Clinical Oncology, 2005
- Two Immunoglobulin G Fragment C Receptor Polymorphisms Independently Predict Response to Rituximab in Patients With Follicular LymphomaJournal of Clinical Oncology, 2003
- Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa geneBlood, 2002