Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma
By M. Chao, Ash A. Alizadeh, Chad Tang, J. Myklebust, B. Varghese, S. Gill, Max Jan, Adriel C. Cha, Charles K Chan, Brent Tan and 10 more. Cell, 2010
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Summary 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.
Subfields: Immunology, Radiology, Nuclear Medicine and Imaging
View Paper: https://www.semanticscholar.org/paper/fa28237500778c1291270ee3a51ddf26aea62eff
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In Immunology
Citations in the corpus
- Cancer immunotherapy via dendritic cells (2012, neutral): “gov/drugdictionary?CdrID=42613">rituximab (a CD20 antibody that depletes B cells) results in enhanced phagocytosis of dead lymphoma cells and improved tumour eradication in mic”
- Progress in tumor-associated macrophage (TAM)-targeted therapeutics (2017, neutral): “However, not all therapies benefit from depletion of macrophages/TAMs, especially immunotherapies designed to stimulate anti-tumor innate immunity [56][57][58].”
- Anti-CD47 antibody–mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response (2013, neutral): “Proc Natl Acad Sci USA 109(17):6662–6667.”