Abstract: The present invention relates to agents and methods that are capable of augmenting NK-mediated killing of target cells by reducing inhibitory KIR signalling without reducing the binding of KIR to HLA-C. As described herein, transduction of negative signaling via KIR, 5 upon binding of KIR to its HLA class I ligand, can involve a ligand-binding induced, conformational reorientation of the KIR molecules allowing interactions to form between adjacent KIRs in specific domains, leading to accelerated clustering. Methods and agents such as mono-clonal antibodies for reducing KIR-mediated inhibition of NK cell cytotoxicity without reducing or blocking HLA-binding by, e.g., reducing or blocking dimerization of KIR, are provided.
Type:
Grant
Filed:
January 6, 2006
Date of Patent:
July 17, 2012
Assignees:
Novo Nordisk A/S, Inmate Pharma S.A.S.
Inventors:
Søren Berg Padkær, Peter Reumert Wagtmann, Pieter Spee, Stefan Zahn, Kristian Kjærgaard