Developing Functional Monoclonal Antibodies for Beta-3 Adrenergic Receptor

G protein-coupled receptors (GPCRs), one of the most commonly used and successful targets for drugs, are a large family of multi-transmembrane proteins and an important class of receptors. Over 40% of all modern medicines interact with this protein group. These cell surface receptors are acted on by a wide variety of ligands, including small molecules and soluble proteins. Monoclonal antibody (mAb) therapy has major advantages over small molecule therapy in that mAbs are more selective and therefore tend to have fewer non-specic or o-target toxicity issues, while having a longer duration of action than small molecule drugs. Unfortunately, it is extremely dicult to create antibodies against GPCRs using traditional approaches, especially for clinical applications. Multispan combines its proprietary immunization technology using its patented GPCR high expression system and in-depth expertise in developing well-designed and validated GPCR functional assays to select mAb leads that perturb disease-relevant signaling pathways. In this poster, we detail the development of Beta-3 adrenergic receptor (β3-AR) mAbs. Our preliminary data showed that several mAb clones specically bound to the receptor while increasing the receptor function by acting as agonists.