Lack of Fucose on Human IgG1 N-Linked Oligosaccharide Improves Binding to Human FcγRIII and Antibody-dependent Cellular Toxicity

Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene

High Resolution Mapping of the Binding Site on Human IgG1 for FcγRI, FcγRII, FcγRIII, and FcRn and Design of IgG1 Variants with Improved Binding to the FcγR

The present invention concerns polypeptides comprising a variant Fc region. More particularly, the present invention concerns Fc region-containing polypeptides that have altered effector function as a consequence of one or more amino acid modifications in the Fc region thereof.

Polypeptide variants with altered effector function

Purpose: Although rituximab is now routinely used in the treatment of B-cell non-Hodgkin’s lymphoma, the mechanism of its antitumor effect is not clear One potential mechanism of action involves antibody-dependent cellular cytotoxicity (ADCC) Two aspects of ADCC influence the effectiveness of this process: the susceptibility of tumor cells and the activation of effector cells via their immunoglobulin G fragment C receptors (FcγRs) Several FcγR polymorphisms have been identified that may affect the killing function of natural killer cells and macrophages Patients and Methods: The pretreatment tumor cells from 43 patients with follicular lymphoma were tested for their intrinsic susceptibility to rituximab-mediated ADCC In addition, the FcγRIIIa (CD16) and FcγRIIa (CD32) polymorphisms were determined in an expanded group of 87 patients The results were then correlated with clinical outcome of these patients Results: No difference was found between the susceptibility of tumors from patients who clinica

Two Immunoglobulin G Fragment C Receptor Polymorphisms Independently Predict Response to Rituximab in Patients With Follicular Lymphoma

https://pure.uva.nl/ws/files/3663177/3046_29021y.pdf

Johan Algra

Papers

FcγRIIIa-158V/F Polymorphism Influences the Binding of IgG by Natural Killer Cell FcγRIIIa, Independently of the FcγRIIIa-48L/R/H Phenotype

FcγRIIIa-158V/F polymorphism influences the binding of IgG by NK cell FcγRIIIa, independent of the FcγRIIIa-48L/R/H phenotype

RIIIa, Independently of the Fc γ Killer Cell Fc RIIIa-158V/F Polymorphism Influences the Binding of IgG by Natural γ Fc