PMID: 9435857Jan 22, 1998Paper

Fc gamma RI blockade and modulation for immunotherapy

Cancer Immunology, Immunotherapy : CII
P K WallaceM W Fanger

Abstract

Splenectomy and corticosteroids are the treatment of choice for patients with immune thrombocytopenic purpura (ITP). However, for the 10%-15% of patients who do not respond to conventional therapy, high-dose i.v. IgG can induce life-saving transient responses. The benefits of i.v. IgG have been attributed to Fc receptor blockade; however, the involvement of the individual Fc receptors for IgG (Fc gamma R) in ITP remain to be more completely defined. Recently a mAb, designated mAb H22, which recognizes an epitope on Fc gamma RI (CD64) outside the ligand-binding domain, was humanized. Because mAb H22 is a human IgG1 and Fc gamma RI has a high affinity for human IgG1 antibodies, we predicted that mAb H22 would bind to the Fc gamma RI ligand-binding site through its Fc domain and to its external Fc gamma RI epitope through both Fab domains. These studies demonstrate that mAb H22 blocked Fc gamma RI-mediated phagocytosis of opsonized red blood cells more effectively than an irrelevant IgG. Moreover, cross-linking Fc gamma RI with mAb H22 down-modulated Fc gamma RI expression on monocytes, an effect seen within 2 h.

Citations

Feb 25, 2010·Annals of Hematology·Markus BiburgerFalk Nimmerjahn
Feb 27, 2001·Journal of Immunological Methods·P K WallaceM W Fanger
Jul 2, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey M BeekmanJeanette H W Leusen
Apr 15, 2005·Molecular Immunology·Réal LemieuxSonia Néron
Jan 11, 2000·Journal of Peptide Science : an Official Publication of the European Peptide Society·J M SheridanB M Austen
Nov 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·C A GuyreM W Fanger

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