Home
Resources
Publications
A Novel Class of anti-IL-12p40 Antibodies: Potent Neutralization via Inhibition of IL-12-IL-12Rβ2 and IL-23-IL-23R

A Novel Class of anti-IL-12p40 Antibodies: Potent Neutralization via Inhibition of IL-12-IL-12Rβ2 and IL-23-IL-23R

Adam W Clarke, Lynn Poulton, Hoi Yi Wai, Stuart A Walker, Shanti David Victor, Teresa Domagala, Dragana Mraovic, Danyal Butt, Nina Shewmaker, Philip Jennings, Anthony G Doyle

MAbs. Sep-Oct 2010;2(5):539-49.

PMID: 20724822

Abstract:

While current therapeutic antibodies bind to IL-12 and IL-23 and inhibit their binding to IL-12Rβ1, we describe a novel antibody, termed 6F6, that binds to IL-12 and IL-23 and inhibits the interaction of IL-12 and IL-23 with their cognate signalling receptors IL-12Rβ2 and IL23R. This antibody does not affect the natural inhibition of the IL-12/23 pathway by the antagonists monomeric IL-12p40 and IL-12p80, which suggests that a dual antagonist system is possible. We have mapped the epitope of 6F6 to domain 3 of the p40 chain common to IL-12 and IL-23 and demonstrate that an antibody bound to this epitope is sufficient to inhibit engagement of the signalling receptors. Antibodies with this unique mechanism of inhibition are potent inhibitors of IL-12 induced IFN-γ production and IL-23 induced IL-17 production in vitro, and in an in vivo model of psoriasis, treatment with a humanized variant of this antibody, h6F6, reduced the inflammatory response, resulting in decreased epidermal hyperplasia. We believe that this new class of IL-12/23 neutralising antibodies has the potential to provide improved potency and efficacy as anti-inflammatory agents, particularly in diseases characterized by an overproduction of IL-12.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248652	IL-12p80 human			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: