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

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

Departament de Medicina

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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. © 2010 Elsevier Inc.

Idioma original	Anglès
Pàgines (de-a)	699-713
Revista	Cell
Volum	142
Número	5
DOIs	https://doi.org/10.1016/j.cell.2010.07.044
Estat de la publicació	Publicada - 3 de set. 2010

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Chao, M. P., Alizadeh, A. A., Tang, C., Myklebust, J. H., Varghese, B., Gill, S., Jan, M., Cha, A. C., Chan, C. K., Tan, B. T., Park, C. Y., Zhao, F., Kohrt, H. E., Malumbres, R., Briones, J., Gascoyne, R. D., Lossos, I. S., Levy, R., Weissman, I. L., & Majeti, R. (2010). Anti-CD47 Antibody Synergizes with Rituximab to Promote Phagocytosis and Eradicate Non-Hodgkin Lymphoma. Cell, 142(5), 699-713. https://doi.org/10.1016/j.cell.2010.07.044

@article{a334fb7063ee486583e3156c501ea849,

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. {\textcopyright} 2010 Elsevier Inc.",

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",

year = "2010",

month = sep,

day = "3",

doi = "10.1016/j.cell.2010.07.044",

language = "English",

volume = "142",

pages = "699--713",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "5",

}

Chao, MP, Alizadeh, AA, Tang, C, Myklebust, JH, Varghese, B, Gill, S, Jan, M, Cha, AC, Chan, CK, Tan, BT, Park, CY, Zhao, F, Kohrt, HE, Malumbres, R, Briones, J, Gascoyne, RD, Lossos, IS, Levy, R, Weissman, IL & Majeti, R 2010, 'Anti-CD47 Antibody Synergizes with Rituximab to Promote Phagocytosis and Eradicate Non-Hodgkin Lymphoma', Cell, vol. 142, núm. 5, pàg. 699-713. https://doi.org/10.1016/j.cell.2010.07.044

TY - JOUR

T1 - Anti-CD47 Antibody Synergizes with Rituximab to Promote Phagocytosis and Eradicate Non-Hodgkin Lymphoma

AU - Chao, Mark P.

AU - Alizadeh, Ash A.

AU - Tang, Chad

AU - Myklebust, June H.

AU - Varghese, Bindu

AU - Gill, Saar

AU - Jan, Max

AU - Cha, Adriel C.

AU - Chan, Charles K.

AU - Tan, Brent T.

AU - Park, Christopher Y.

AU - Zhao, Feifei

AU - Kohrt, Holbrook E.

AU - Malumbres, Raquel

AU - Briones, Javier

AU - Gascoyne, Randy D.

AU - Lossos, Izidore S.

AU - Levy, Ronald

AU - Weissman, Irving L.

AU - Majeti, Ravindra

PY - 2010/9/3

Y1 - 2010/9/3

N2 - 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. © 2010 Elsevier Inc.

AB - 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. © 2010 Elsevier Inc.

KW - Cellimmuno

KW - Humdisease

UR - https://www.scopus.com/pages/publications/77956150056

U2 - 10.1016/j.cell.2010.07.044

DO - 10.1016/j.cell.2010.07.044

M3 - Article

SN - 0092-8674

VL - 142

SP - 699

EP - 713

JO - Cell

JF - Cell

IS - 5

ER -

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

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