@article{bccef1fa18e248e2a88a7b4434f74a5b,
title = "Anti-CD47 Antibody Synergizes with Rituximab to Promote Phagocytosis and Eradicate Non-Hodgkin Lymphoma",
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.",
keywords = "Cellimmuno, Humdisease",
author = "Chao, {Mark P.} and Alizadeh, {Ash A.} and Chad Tang and Myklebust, {June H.} and Bindu Varghese and Saar Gill and Max Jan and Cha, {Adriel C.} and Chan, {Charles K.} and Tan, {Brent T.} and Park, {Christopher Y.} and Feifei Zhao and Kohrt, {Holbrook E.} and Raquel Malumbres and Javier Briones and Gascoyne, {Randy D.} and Lossos, {Izidore S.} and Ronald Levy and Weissman, {Irving L.} and Ravindra Majeti",
note = "Funding Information: The authors acknowledge Dr. Christopher Contag for providing luciferase constructs, Dr. Robert Negrin for assistance, Dr. Yaso Natkunam for immunohistochemistry, Libuse Jerabek and Theresa Storm for lab management, and Adriane Mosely for animal husbandry. We also acknowledge the patients and surgeons including Drs. Wapnir, Chang, Cheng, Janisiewicz, Koltai, Liebowitz, and Messner for providing research specimens. M.P.C. is supported by the HHMI and the Stanford Cancer Biology Program, A.A.A. by an NIH T32 Ruth L. Kirschstein National Research Service Award (HL007970), R. Malumbres by a fellowship from Fundaci{\'o}n Caja Madrid, I.S.L. by NIH grant CA122105, and R. Majeti by a grant from the AACR. R. Majeti holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. I.L.W., M.P.C., A.A.A., and R. Majeti have filed U.S. Patent Application Serial No. 12/321,215 entitled “Methods For Manipulating Phagocytosis Mediated by CD47.” This research is supported by NIH grant P01CA139490 to I.L.W. and funding from the Smith Family Fund. ",
year = "2010",
month = sep,
day = "3",
doi = "10.1016/j.cell.2010.07.044",
language = "English (US)",
volume = "142",
pages = "699--713",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}
