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Anti-CD47 Antibody Synergizes with Rituximab to Promote Phagocytosis and Eradicate Non-Hodgkin Lymphoma

  作者 Chao, MP; Alizadeh, AA; Tang, C; Myklebust, JH; Varghese, B; Gill, S; Jan, M; Cha, AC; Chan, CK; Tan, BT; Park, CY; Zhao, FF; Kohrt, HE; Malumbres, R; Briones, J; Gascoyne, RD; Lossos, IS; Levy, R; Weissman, IL; Majeti, R  
  选自 期刊  Cell;  卷期  2010年142-5;  页码  699-713  
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[摘要]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.

 
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