Anne-Laure Gagez1, Guillaume Cartron. 1. aUMR CNRS 5235, Université Montpellier, Montpellier bLabex MAbImprove, Faculté de Médecine de Tours, Tours cDépartement d'Hématologie Clinique, Centre Hospitalier Régional Universitaire (CHRU) de Montpellier, Montpellier, France.
Abstract
PURPOSE OF REVIEW: Obinutuzumab is a new anti-CD20 monoclonal antibody which demonstrated clinical superiority compared with rituximab in a recent phase III study. There is a need to better understand how this antibody differs from rituximab and why it could modify the landscape of the treatment of CD20 malignancies in the near future. RECENT FINDINGS: Antibody-dependent cellular cytotoxicity plays a critical role in clinical activity of rituximab. To increase antibody-dependent cellular cytotoxicity, a strategy improving the affinity between the Fc portion of the antibody and FcγRIIIa expressed by effector cells has been recently developed. This strategy modifies the carbohydrate located between the two Fc arms. Thus, the lack of fucose on IgG oligosaccharide improves binding to FcγRIII and antibody-dependent cellular cytotoxicity. Obinutuzumab recognized a CD20 epitope different from that bound by rituximab. This property confers different features to obinutuzumab mechanisms of action with a noncaspase-dependent direct-cell death and the lack of complement-dependent cytotoxicity. Obinutuzumab demonstrated significant activity in animal models, and phase I or II studies showed clinical activity in different subtypes of CD20 diseases. SUMMARY: Obinutuzumab, a type II glycoengineered monoclonal antibody, is characterized by an increased antibody-dependent cellular cytotoxicity and direct-cell death but no complement-dependent cytotoxicity. Recent clinical data demonstrated a superiority of obinutuzumab compared with rituximab, suggesting that this antibody should be, in the future, the backbone of the treatment of B-lymphoproliferative disorders.
PURPOSE OF REVIEW: Obinutuzumab is a new anti-CD20 monoclonal antibody which demonstrated clinical superiority compared with rituximab in a recent phase III study. There is a need to better understand how this antibody differs from rituximab and why it could modify the landscape of the treatment of CD20malignancies in the near future. RECENT FINDINGS: Antibody-dependent cellular cytotoxicity plays a critical role in clinical activity of rituximab. To increase antibody-dependent cellular cytotoxicity, a strategy improving the affinity between the Fc portion of the antibody and FcγRIIIa expressed by effector cells has been recently developed. This strategy modifies the carbohydrate located between the two Fc arms. Thus, the lack of fucose on IgG oligosaccharide improves binding to FcγRIII and antibody-dependent cellular cytotoxicity. Obinutuzumab recognized a CD20 epitope different from that bound by rituximab. This property confers different features to obinutuzumab mechanisms of action with a noncaspase-dependent direct-cell death and the lack of complement-dependent cytotoxicity. Obinutuzumab demonstrated significant activity in animal models, and phase I or II studies showed clinical activity in different subtypes of CD20 diseases. SUMMARY:Obinutuzumab, a type II glycoengineered monoclonal antibody, is characterized by an increased antibody-dependent cellular cytotoxicity and direct-cell death but no complement-dependent cytotoxicity. Recent clinical data demonstrated a superiority of obinutuzumab compared with rituximab, suggesting that this antibody should be, in the future, the backbone of the treatment of B-lymphoproliferative disorders.
Authors: Fleur S van de Bovenkamp; Ninotska I L Derksen; Pleuni Ooijevaar-de Heer; Karin A van Schie; Simone Kruithof; Magdalena A Berkowska; C Ellen van der Schoot; Hanna IJspeert; Mirjam van der Burg; Ann Gils; Lise Hafkenscheid; René E M Toes; Yoann Rombouts; Rosina Plomp; Manfred Wuhrer; S Marieke van Ham; Gestur Vidarsson; Theo Rispens Journal: Proc Natl Acad Sci U S A Date: 2018-02-05 Impact factor: 11.205
Authors: John Zhai; Yan Qin; Jun Zhu; Yuqin Song; Zhixiang Shen; Xin Du; Candice Jamois; Michael Brewster; Yuankai Shi; Jun Shi Journal: Br J Clin Pharmacol Date: 2017-02-14 Impact factor: 4.335