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

Mark P Chao; 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

doi:10.1016/j.cell.2010.07.044

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

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

Mark P Chao, Ash A Alizadeh, Chad Tang, June H Myklebust, Bindu Varghese, Saar Gill, Max Jan, Adriel C Cha, Charles K Chan, Brent T Tan, …

Cell (Cambridge), Vol.142(5), pp.699-713

2010-09-03

DOI: https://doi.org/10.1016/j.cell.2010.07.044

PMCID: PMC2943345

PMID: 20813259

Abstract

HUMDISEASE

CELLIMMUNO

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. [Display omitted] ► CD47 is a prognostic factor and therapeutic target in non-Hodgkin Lymphoma (NHL) ► Anti-CD47 antibody synergizes with rituximab to eradicate NHL in vitro and in vivo ► Antibody synergy occurs by Fc receptor-independent and -dependent mechanisms ► Anti-CD47 mAb synergy with FcR-activating mAbs may be applicable to other cancers

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.132 Extracellular Matrix & Cell Differentiation; 1.132.1868 Osteopontin
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology
ESI research areas: Molecular Biology & Genetics

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Title: Anti-CD47 Antibody Synergizes with Rituximab to Promote Phagocytosis and Eradicate Non-Hodgkin Lymphoma
Creators: Mark P Chao - Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, and Ludwig Center at Stanford, Stanford University, Palo Alto, CA 94304, USA
Ash A Alizadeh - Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, and Ludwig Center at Stanford, Stanford University, Palo Alto, CA 94304, USA
Chad Tang - Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, and Ludwig Center at Stanford, Stanford University, Palo Alto, CA 94304, USA
June H Myklebust - Division of Oncology, Stanford University, Palo Alto, CA 94304, USA
Bindu Varghese - Division of Oncology, Stanford University, Palo Alto, CA 94304, USA
Saar Gill - Division of Blood and Bone Marrow Transplantation, Stanford University, Palo Alto, CA 94304, USA
Max Jan - Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, and Ludwig Center at Stanford, Stanford University, Palo Alto, CA 94304, USA
Adriel C Cha - Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, and Ludwig Center at Stanford, Stanford University, Palo Alto, CA 94304, USA
Charles K Chan - Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, and Ludwig Center at Stanford, Stanford University, Palo Alto, CA 94304, USA
Brent T Tan - Department of Pathology, Stanford University, Palo Alto, CA 94304, USA
Christopher Y Park - Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, and Ludwig Center at Stanford, Stanford University, Palo Alto, CA 94304, USA
Feifei Zhao - Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, and Ludwig Center at Stanford, Stanford University, Palo Alto, CA 94304, USA
Holbrook E Kohrt - Department of Internal Medicine, Division of Hematology, Stanford University, Palo Alto, CA 94304, USA
Raquel Malumbres - Department of Medicine, Division of Hematology-Oncology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Javier Briones - Department of Hematology, Hospital Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona 08193, Spain
Randy D Gascoyne - Department of Pathology, British Columbia Cancer Agency, Vancouver V5Z 1L3, Canada
Izidore S Lossos - Department of Medicine, Division of Hematology-Oncology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Ronald Levy - Division of Oncology, Stanford University, Palo Alto, CA 94304, USA
Irving L Weissman - Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, and Ludwig Center at Stanford, Stanford University, Palo Alto, CA 94304, USA
Ravindra Majeti - Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, and Ludwig Center at Stanford, Stanford University, Palo Alto, CA 94304, USA
Publication Details: Cell (Cambridge), Vol.142(5), pp.699-713
Publisher: Elsevier Inc
Academic Unit: Miller School of Medicine; UMMG Dept of Medicine - Hematology/Oncology
Language: English
Resource Type: Journal article
PMID: 20813259
PMCID: PMC2943345
Record Identifier: 991031559439002976