Author/Authors :
Mark P. Chao، نويسنده , , Ash A. Alizadeh، نويسنده , , Chad Tang، نويسنده , , June H. Myklebust، نويسنده , , Bindu Varghese، نويسنده , , Saar Gill، نويسنده , , Max Jan، نويسنده , , Adriel C. Cha، نويسنده , , Charles K. Chan، نويسنده , , Brent T. Tan، نويسنده , , Christopher Y. Park، نويسنده , , Feifei Zhao، نويسنده , , Holbrook E. Kohrt، نويسنده , , Raquel Malumbres، نويسنده , , Javier Briones، نويسنده , , Randy D. Gascoyne، نويسنده , , Izidore S. Lossos، نويسنده , , Ronald Levy، نويسنده , , Irving L. Weissman، نويسنده , , Ravindra Majeti، نويسنده , , et al.، نويسنده ,
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.
