Novo Nordisk A/s

Innate Pharma S.a.s.

University of Genoa

Inmate Pharma S.a.s.

Innate Pharma

Universita Di Genova

Pieter Spee

Stefan Zahn

Søren Berg Padkær

Peter Andreas Nicolai Reumert Wagtmann

Anders Svensson

Kristian Kjærgaard

Laurent Gauthier

Alessandro Moretta

Pascale Andre

Kristian Kjaergaard

Francois Romagne

Mariella Della Chiesa

Ivan Svendsen

Francois Romagné

Michael Wilken

Søren Berg Padkjær

Peter Reumert Wagtmann

Matthias Thórólfsson

François Romagne

Soren Berg Padkaer

Søren Berg Padkaer

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, 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 monoclonal 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.

KIR-binding agents and methods of use thereof

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.

Compositions and methods for regulating an immune response in a subject are described. More particularly, described are human antibodies that regulate the activity of NK cells and allow a potentiation of NK cell cytotoxicity in mammalian subjects, and antibodies having antigen-binding properties similar to those of human monoclonal antibody 1-7F9 or 1-4F1. Described also are also fragments and derivatives of such antibodies, as well as pharmaceutical compositions comprising the same and their uses, particularly for use in therapy, to increase NK cell activity or cytotoxicity in subjects.

Human anti-KIR antibodies

Growing community of inventors

Allerød, Denmark

Pieter Spee