Ratanatharathorn Voravit, Pavletic Steven, Uberti Joseph P
Blood and Marrow Stem Cell Transplantation Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Cancer Treat Rev. 2009 Dec;35(8):653-61. doi: 10.1016/j.ctrv.2009.07.004. Epub 2009 Aug 13.
Rituximab is a chimeric monoclonal antibody directed against CD20, a B-cell antigen expressed on B-cell lymphoma. It is widely used as single agent for the treatment of follicular lymphoma or in conjunction with other combination therapy as frontline or salvage therapy. Its efficiency in B-cell depletion has lead to other applications such as therapy for autoimmune diseases, GVHD and other immunologic complications in allogeneic stem cell transplantation. Clinical responses to rituximab unveiled the role of B-cells in the pathogenesis of these disorders. Attenuation of pathogenic antibody production partly explained the clinical response in patients with autoimmune disease and chronic GVHD, but other immune mechanisms might be operative as well. Expansion of regulatory T-cells (Tregs) following rituximab therapy indicated the interaction of T- and B-cells in chronic GVHD. Therefore, effort to maintain expansion of Tregs might be important for long-term control of these diseases. Other B-cell targeting strategy directing against B-cell-activating factor (BAFF) or its receptor could be considered in conjunction with rituximab. Recent CIBMTR data on reduced cumulative incidence of acute GVHD in patients who had prior rituximab also suggest the early role of B-cells in allogeneic transplantation, thus opening the opportunity for further immune modulation to prevent acute GVHD.
利妥昔单抗是一种针对CD20的嵌合单克隆抗体，CD20是一种在B细胞淋巴瘤上表达的B细胞抗原。它被广泛用作治疗滤泡性淋巴瘤的单一药物，或与其他联合疗法一起作为一线或挽救疗法。其在清除B细胞方面的有效性已导致了其他应用，如治疗自身免疫性疾病、移植物抗宿主病（GVHD）以及异基因干细胞移植中的其他免疫并发症。对利妥昔单抗的临床反应揭示了B细胞在这些疾病发病机制中的作用。致病性抗体产生的减弱部分解释了自身免疫性疾病和慢性GVHD患者的临床反应，但其他免疫机制可能也起作用。利妥昔单抗治疗后调节性T细胞（Tregs）的扩增表明了T细胞和B细胞在慢性GVHD中的相互作用。因此，努力维持Tregs的扩增可能对这些疾病的长期控制很重要。可以考虑将针对B细胞活化因子（BAFF）或其受体的其他靶向B细胞策略与利妥昔单抗联合使用。国际骨髓移植登记处（CIBMTR）最近关于先前使用利妥昔单抗的患者急性GVHD累积发病率降低的数据也表明了B细胞在异基因移植中的早期作用，从而为进一步的免疫调节以预防急性GVHD提供了机会。
