Therapeutic Activity of Humanized Anti-CD20 Monoclonal Antibody and Polymorphism in IgG FcReceptor FcgRIIIa Gene
March 01, 2002ByG. Cartron|L. Dacheux|G. Salles|P. Solal-Celigny|P. Bardos|P. Colombat|H. Watier
Rituximab (Rituxan) is a chimeric IgG1 anti-CD20 monoclonal antibody increasingly used in the treatment of non-Hodgkin’s lymphoma (NHL). Previous in vitro studies have suggested the role of antibody-dependent cellular cytotoxicity (ADCC) and FcgR-positive effector cells (natural killer and macrophage) in the antitumor effects of anti-CD20 antibodies, but the actual mechanism of rituximab action in vivo remains largely unknown. The FCGR3A gene coding for the FcgRIIIa receptor displays a functional dimorphism with either a phenylalanine (FCGR3A-158F) or a valine (FCGR3A-158V) at amino acid 158, with a higher affinity of human IgG1 and increased ADCC for the latter. The aim of this study was thus to determine the influence of this FCGR3A polymorphism on clinical and molecular responses to rituximab.