[HTML][HTML] Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma

MP Chao, AA Alizadeh, C Tang, JH Myklebust… - Cell, 2010 - cell.com
MP Chao, AA Alizadeh, C Tang, JH Myklebust, B Varghese, S Gill, M Jan, AC Cha, CK Chan
Cell, 2010cell.com
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 …
Summary
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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