Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, and Ludwig Center at Stanford, Stanford University, Palo Alto, CA 94304, USA.
Cell. 2010 Sep 3;142(5):699-713. doi: 10.1016/j.cell.2010.07.044.
Monoclonal antibodies are standard therapeutics for several cancers including the anti-CD20 antibody rituximab for B cell non-Hodgkin lymphoma (NHL). Rituximab and other antibodies are not curative and must be combined with cytotoxic chemotherapy for clinical benefit. Here we report the eradication of human NHL solely with a monoclonal antibody therapy combining rituximab with a blocking anti-CD47 antibody. We identified increased expression of CD47 on human NHL cells and determined that higher CD47 expression independently predicted adverse clinical outcomes in multiple NHL subtypes. Blocking anti-CD47 antibodies preferentially enabled phagocytosis of NHL cells and synergized with rituximab. Treatment of human NHL-engrafted mice with anti-CD47 antibody reduced lymphoma burden and improved survival, while combination treatment with rituximab led to elimination of lymphoma and cure. These antibodies synergized through a mechanism combining Fc receptor (FcR)-dependent and FcR-independent stimulation of phagocytosis that might be applicable to many other cancers.
单克隆抗体是多种癌症的标准治疗药物，包括抗 CD20 抗体利妥昔单抗治疗 B 细胞非霍奇金淋巴瘤（NHL）。利妥昔单抗和其他抗体并非治愈性的，必须与细胞毒性化疗联合使用才能获得临床益处。在这里，我们报告了一种仅用单克隆抗体疗法联合利妥昔单抗和一种阻断抗 CD47 抗体即可根除人类 NHL。我们发现人类 NHL 细胞上 CD47 的表达增加，并确定更高的 CD47 表达独立预测多种 NHL 亚型的不良临床结局。阻断抗 CD47 抗体优先使 NHL 细胞被吞噬，并与利妥昔单抗协同作用。用抗 CD47 抗体治疗人 NHL 移植小鼠可减少淋巴瘤负担并提高生存率，而与利妥昔单抗联合治疗可导致淋巴瘤消除和治愈。这些抗体通过一种机制协同作用，该机制结合了 Fc 受体（FcR）依赖性和 FcR 非依赖性吞噬刺激，可能适用于许多其他癌症。
