| Literature DB >> 20813259 |
Mark P Chao1, Ash A Alizadeh, Chad Tang, June H Myklebust, Bindu Varghese, Saar Gill, Max Jan, Adriel C Cha, Charles K Chan, Brent T Tan, Christopher Y Park, Feifei Zhao, Holbrook E Kohrt, Raquel Malumbres, Javier Briones, Randy D Gascoyne, Izidore S Lossos, Ronald Levy, Irving L Weissman, Ravindra Majeti.
Abstract
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. Copyright 2010 Elsevier Inc. All rights reserved.Entities:
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Year: 2010 PMID： 20813259 PMCID： PMC2943345 DOI： 10.1016/j.cell.2010.07.044
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582