P2X3 is a validated therapeutic target for pain, but its structural complexity has made it difficult to target using small molecules, and previous approaches using such drugs have failed due to the lack of compound specificity and limited bioavailability. Monoclonal antibodies (MAbs) offer superior specificity and bioavailability, which are paramount to the successful therapeutic inhibition of many membrane protein targets. Thorough characterization of the P2X3 MAbs reveals that they bind conformational epitopes on P2X3 with high specificity and sub-nanomolar affinity. The MAbs also block 90% of neuronal currents in primary cells ex vivo, enabling further development of lead candidates.
“We are extremely excited to have generated inhibitory MAbs that target P2X3. This is an exciting advancement for the chronic pain field where there are limited therapeutic options,” said
The antibodies were elicited using Integral Molecular’s Lipoparticle reagents, which provide highly concentrated membrane proteins in their native conformation, and were screened using Crystal Bioscience’s GEM technology.
“The recovery of antibodies with these unique characteristics confirms and extends our previous results, showing that the immunoglobulin repertoire of immunized chickens contains antibodies to epitopes that cannot be accessed using conventional discovery platforms. These data are also a testament to the power of the GEM technology to screen the repertoire and identify antibodies that not only bind the target but are biologically active,” said
About Integral Molecular
Integral Molecular is a research-driven biotechnology company creating a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, and transporters, using its proprietary MPS Discovery Engine™. This platform is built on the company’s Lipoparticle and Shotgun Mutagenesis technologies as well as its 10+ years of experience optimizing membrane proteins, enabling the isolation, characterization, and engineering of monoclonal antibodies against otherwise intractable membrane protein targets. The company currently has therapeutic programs focused on pain, cancer, and infectious diseases.
About Crystal Bioscience
Crystal Bioscience is a privately held company that was founded in 2008 to develop a world-class therapeutic antibody discovery engine. Its platform is “powered by evolution,” exploiting the large phylogenetic distance between mammals and birds to generate a diverse array of antibodies to human targets that have proven intractable in mammalian and other discovery platforms. Crystal’s patented platform provides the unique ability to isolate monoclonal antibodies from immunized chickens, and can screen simultaneously for specificity and biological activity. It has led to the discovery of bioactive monoclonals directed against difficult targets, including GPCRs and ion channels. Chicken antibodies often recognize both human and mouse orthologs, which can simplify early stages of drug development where mouse disease models are used. The depth of screening provided by the GEM assay in combination with the breadth of the antibody repertoire in immunized birds provides access to an unparalleled source of affinity matured antibodies with therapeutic potential.
Source: Integral Molecular
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