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

Research output: Contribution to journalArticle

430 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)699-713
Number of pages15
JournalCell
Volume142
Issue number5
DOIs
StatePublished - Sep 3 2010

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Keywords

  • Cellimmuno
  • Humdisease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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