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

被引：924

作者：

Chao, Mark P. ^{[1
,2
]}

Alizadeh, Ash A. ^{[1
,2
,3
,4
]}

Tang, Chad ^{[1
,2
]}

Myklebust, June H. ^{[4
,10
]}

Varghese, Bindu ^{[4
]}

Gill, Saar ^{[6
]}

Jan, Max ^{[1
,2
]}

Cha, Adriel C. ^{[1
,2
]}

Chan, Charles K. ^{[1
,2
]}

Tan, Brent T. ^{[5
]}

Park, Christopher Y. ^{[1
,2
,5
]}

Zhao, Feifei ^{[1
,2
]}

Kohrt, Holbrook E. ^{[3
,4
]}

Malumbres, Raquel ^{[7
]}

Briones, Javier ^{[8
]}

Gascoyne, Randy D. ^{[9
]}

Lossos, Izidore S. ^{[7
]}

Levy, Ronald ^{[4
]}

Weissman, Irving L. ^{[1
,2
,5
]}

Majeti, Ravindra ^{[1
,2
,3
]}

机构：

[1] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford Canc Ctr, Palo Alto, CA 94304 USA

[2] Stanford Univ, Ludwig Ctr Stanford, Palo Alto, CA 94304 USA

[3] Stanford Univ, Dept Internal Med, Div Hematol, Palo Alto, CA 94304 USA

[4] Stanford Univ, Div Oncol, Palo Alto, CA 94304 USA

[5] Stanford Univ, Dept Pathol, Palo Alto, CA 94304 USA

[6] Stanford Univ, Div Blood & Bone Marrow Transplantat, Palo Alto, CA 94304 USA

[7] Univ Miami, Miller Sch Med, Div Hematol Oncol, Dept Med, Miami, FL 33136 USA

[8] Autonomous Univ Barcelona, Hosp Santa Creu & St Pau, Dept Hematol, E-08193 Barcelona, Spain

[9] British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 1L3, Canada

[10] Univ Oslo, Inst Canc Res, Dept Immunol, Oslo Univ Hosp,Ctr Canc Biomed, N-0310 Oslo, Norway

来源：

CELL | 2010年 / 142卷 / 05期

关键词：

B-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; DRUG-COMBINATION; CD20; EXPRESSION; CD47; THERAPY; MECHANISMS;

D O I：

10.1016/j.cell.2010.07.044

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：699 / 713

页数：15

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