The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

被引：1292

作者：

Willingham, Stephen B. ^{[1
,2
]}

Volkmer, Jens-Peter ^{[1
,2
,3
]}

Gentles, Andrew J. ^{[4
]}

Sahoo, Debashis ^{[1
,2
]}

Dalerba, Piero ^{[1
,2
,5
]}

Mitra, Siddhartha S. ^{[1
,2
]}

Wang, Jian ^{[12
,13
,14
]}

Contreras-Trujillo, Humberto ^{[1
,2
]}

Martin, Robin ^{[1
,2
]}

Cohen, Justin D. ^{[1
,2
]}

Lovelace, Patricia ^{[1
,2
]}

Scheeren, Ferenc A. ^{[1
,2
]}

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

Weiskopf, Kipp ^{[1
,2
]}

Tang, Chad ^{[1
,2
]}

Volkmer, Anne Kathrin ^{[1
,2
]}

Naik, Tejaswitha J. ^{[1
,2
]}

Storm, Theresa A. ^{[1
,2
]}

Mosley, Adriane R. ^{[1
,2
]}

Edris, Badreddin ^{[1
,2
]}

Schmid, Seraina M. ^{[16
]}

Sun, Chris K. ^{[6
]}

Chua, Mei-Sze ^{[6
]}

Murillo, Oihana ^{[1
,2
]}

Rajendran, Pradeep ^{[1
,2
]}

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

Chin, Robert K. ^{[1
,2
,15
]}

Kim, Dongkyoon ^{[1
,2
]}

Adorno, Maddalena ^{[1
,2
]}

Raveh, Tal ^{[1
,2
]}

Tseng, Diane ^{[1
,2
]}

Jaiswal, Siddhartha ^{[1
,2
]}

Enger, Per Oyvind ^{[12
,13
,14
]}

Steinberg, Gary K. ^{[7
]}

Li, Gordon ^{[7
]}

So, Samuel K. ^{[6
]}

Majeti, Ravindra ^{[1
,2
,8
]}

Harsh, Griffith R. ^{[9
,15
]}

van de Rijn, Matt ^{[10
]}

Teng, Nelson N. H. ^{[11
]}

Sunwoo, John B. ^{[1
,2
,9
]}

Alizadeh, Ash A. ^{[1
,2
,8
]}

Clarke, Michael F. ^{[1
,2
,5
]}

Weissman, Irving L. ^{[1
,2
,10
]}

机构：

[1] Stanford Univ, Med Ctr, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[2] Stanford Univ, Med Ctr, Ludwig Canc Ctr, Stanford, CA 94305 USA

[3] Stanford Univ, Med Ctr, Dept Urol, Stanford, CA 94305 USA

[4] Stanford Univ, Med Ctr, Stanford Res Initiat Syst Biol Canc, Stanford, CA 94305 USA

[5] Stanford Univ, Med Ctr, Dept Internal Med, Div Oncol, Stanford, CA 94305 USA

[6] Stanford Univ, Med Ctr, Asian Liver Ctr, Stanford, CA 94305 USA

[7] Stanford Univ, Med Ctr, Dept Neurosurg, Stanford, CA 94305 USA

[8] Stanford Univ, Med Ctr, Dept Internal Med, Div Hematol, Stanford, CA 94305 USA

[9] Stanford Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Stanford, CA 94305 USA

[10] Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA

[11] Stanford Univ, Med Ctr, Dept Obstet & Gynecol, Stanford, CA 94305 USA

[12] Haukeland Hosp, Dept Neurosurg, N-5021 Bergen, Norway

[13] Univ Bergen, Dept Biomed, N-5009 Bergen, Norway

[14] Univ Bergen, Dept Neurosurg, N-5009 Bergen, Norway

[15] Stanford Univ, Med Ctr, Dept Radiat Oncol, Stanford, CA 94305 USA

[16] Univ Womens Hosp Basel, Dept Obstet & Gynecol, CH-4031 Basel, Switzerland

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 17期

关键词：

INTEGRIN-ASSOCIATED PROTEIN; CELL-SURFACE CALRETICULIN; GENE-EXPRESSION; APOPTOTIC CELLS; STEM-CELLS; OVARIAN-CANCER; CD47; MACROPHAGES; RECEPTOR; PHAGOCYTOSIS;

D O I：

10.1073/pnas.1121623109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival formultiple types of cancer. CD47 is a ligand for SIRP alpha, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.

引用

页码：6662 / 6667

页数：6

共 48 条

[1] INTRATUMORAL INJECTION OF AN ADENOVIRUS EXPRESSING INTERLEUKIN-2 INDUCES REGRESSION AND IMMUNITY IN A MURINE BREAST-CANCER MODEL [J].

ADDISON, CL ;

BRACIAK, T ;

RALSTON, R ;

MULLER, WJ ;

GAULDIE, J ;

GRAHAM, FL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (18) :8522-8526

[2] The inflammatory micro-environment in tumor progression: The role of tumor-associated macrophages [J].

Allavena, Paola ;

Sica, Antonio ;

Solinas, Graziella ;

Porta, Chiara ;

Mantovani, Alberto .

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2008, 66 (01) :1-9

[3] CD47 (integrin-associated protein) engagement of dendritic cell and macrophage counterreceptors is required to prevent the clearance of donor lymphohematopoietic cells [J].

Blazar, BR ;

Lindberg, FP ;

Ingulli, E ;

Panoskaltsis-Mortari, A ;

Oldenborg, PA ;

Iizuka, K ;

Yokoyama, WM ;

Taylor, PA .

JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (04) :541-549

[4] INTEGRIN-ASSOCIATED PROTEIN - A 50-KD PLASMA-MEMBRANE ANTIGEN PHYSICALLY AND FUNCTIONALLY ASSOCIATED WITH INTEGRINS [J].

BROWN, E ;

HOOPER, L ;

HO, T ;

GRESHAM, H .

JOURNAL OF CELL BIOLOGY, 1990, 111 (06) :2785-2794

[5] Integrin-associated protein (CD47) and its ligands [J].

Brown, EJ ;

Frazier, WA .

TRENDS IN CELL BIOLOGY, 2001, 11 (03) :130-135

[6] Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells [J].

Chan, Keith Syson ;

Espinosa, Inigo ;

Chao, Mark ;

Wong, David ;

Ailles, Laurie ;

Diehn, Max ;

Gill, Harcharan ;

Presti, Joseph, Jr. ;

Chang, Howard Y. ;

van de Rijn, Matt ;

Shortliffe, Linda ;

Weissman, Irving L. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (33) :14016-14021

[7] Calreticulin Is the Dominant Pro-Phagocytic Signal on Multiple Human Cancers and Is Counterbalanced by CD47 [J].

Chao, Mark P. ;

Jaiswal, Siddhartha ;

Weissman-Tsukamoto, Rachel ;

Alizadeh, Ash A. ;

Gentles, Andrew J. ;

Volkmer, Jens ;

Weiskopf, Kipp ;

Willingham, Stephen B. ;

Raveh, Tal ;

Park, Christopher Y. ;

Majeti, Ravindra ;

Weissman, Irving L. .

SCIENCE TRANSLATIONAL MEDICINE, 2010, 2 (63)

[8] Anti-CD47 Antibody Synergizes with Rituximab to Promote Phagocytosis and Eradicate Non-Hodgkin Lymphoma [J].

Chao, Mark P. ;

Alizadeh, Ash A. ;

Tang, Chad ;

Myklebust, June H. ;

Varghese, Bindu ;

Gill, Saar ;

Jan, Max ;

Cha, Adriel C. ;

Chan, Charles K. ;

Tan, Brent T. ;

Park, Christopher Y. ;

Zhao, Feifei ;

Kohrt, Holbrook E. ;

Malumbres, Raquel ;

Briones, Javier ;

Gascoyne, Randy D. ;

Lossos, Izidore S. ;

Levy, Ronald ;

Weissman, Irving L. ;

Majeti, Ravindra .

CELL, 2010, 142 (05) :699-713

[9] Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression [J].

Chung, CH ;

Parker, JS ;

Karaca, G ;

Wu, JY ;

Funkhouser, WK ;

Moore', D ;

Butterfoss, D ;

Xiang, D ;

Zonation, A ;

Yin, XY ;

Shockley, WW ;

Weissler, MC ;

Dressler, LG ;

Shores, CG ;

Yarbrough, WG ;

Perou, CM .

CANCER CELL, 2004, 5 (05) :489-500

[10] Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets [J].

Clynes, RA ;

Towers, TL ;

Presta, LG ;

Ravetch, JV .

NATURE MEDICINE, 2000, 6 (04) :443-446

← 1 2 3 4 5 →