Gagez Anne-Laure, Cartron Guillaume
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.
Curr Opin Oncol. 2014 Sep;26(5):484-91. doi: 10.1097/CCO.0000000000000107.
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.
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.
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.
奥滨尤妥珠单抗是一种新型抗CD20单克隆抗体，在最近的一项III期研究中显示出比利妥昔单抗更具临床优势。有必要更好地了解这种抗体与利妥昔单抗有何不同，以及为何它可能在不久的将来改变CD20恶性肿瘤的治疗格局。
抗体依赖性细胞毒性在利妥昔单抗的临床活性中起关键作用。为了增强抗体依赖性细胞毒性，最近开发了一种提高抗体Fc段与效应细胞表达的FcγRIIIa之间亲和力的策略。该策略修饰了位于两条Fc臂之间的碳水化合物。因此，IgG寡糖上缺乏岩藻糖可改善与FcγRIII的结合以及抗体依赖性细胞毒性。奥滨尤妥珠单抗识别的CD20表位与利妥昔单抗结合的表位不同。这一特性赋予奥滨尤妥珠单抗不同的作用机制特点，即非半胱天冬酶依赖性直接细胞死亡且缺乏补体依赖性细胞毒性。奥滨尤妥珠单抗在动物模型中显示出显著活性，I期或II期研究表明其在不同亚型的CD20疾病中具有临床活性。
奥滨尤妥珠单抗是一种II型糖工程单克隆抗体，其特点是抗体依赖性细胞毒性增加和直接细胞死亡，但无补体依赖性细胞毒性。最近的临床数据表明奥滨尤妥珠单抗比利妥昔单抗更具优势，这表明该抗体在未来应成为B淋巴细胞增殖性疾病治疗的支柱。
