The Need
P2X7 is a ligand-gated ion channel that can be targeted for anti-inflammatory and anti-cancer therapeutics. P2X7 activity is important for the activation of inflammation through the inflammasome and additionally regulates the metabolism of resident memory T cells which are drivers for many autoimmune diseases. MAbs against this target may be valuable for treating atopic dermatitis, glomerulonephritis, and other autoimmune diseases. MAb therapy is a promising modality to target P2X7, but generating functional antibodies against this complex, trimeric, multispanning ion channel has been a challenge.
The Solution
P2X7 antibodies were isolated using Integral Molecular's MPS Antibody Discovery platform, which uses proprietary DNA and Lipoparticle immunization technologies to display native-conformation immunogen. Evolutionarily divergent animals (chickens) were used as the immunization host in order to generate a robust immune response that delivered 198 different MAbs across 31 unique antibody families.
Specificity profiling against> 5,300 membrane proteins showed P2X7 MAbs to have exquisite specificity for their target and to lack reactivity against other proteins.
%20(6).png "Antibody Specificity Profiling P2X7 graph")
The Impact
Functional P2X7 MAbs
MPS technologies enabled the successful discovery of 6 P2X7-specific antagonist antibodies and 1 rare P2X7 agonist antibody that all bound with picomolar affinities. The antibodies were shown to bind to endogenous P2X7 on the surface of peripheral blood mononuclear cells (PBMCs). There are no currently approved drugs against this target and Integral Molecular is advancing a panel of P2X7 antibodies toward preclinical development for autoimmune and cancer therapeutics.
%20(3).png?width=330&height=307&name=PDF%20images%20for%20website%20(330%20%C3%97%20307%20px)%20(3).png "P2X7 antagonist")
%20(2).png?width=330&height=307&name=PDF%20images%20for%20website%20(330%20%C3%97%20307%20px)%20(2).png "P2X7 agonist")