GPCR targeting antibodies

GPCRs are a large family of seven-transmembrane proteins that share broad conformational similarities but play very diverse functions in a wide variety of cellular processes.  The major part of the GPCR proteins is embedded in the plasma membrane, exposing only relatively small regions to each side of the cell membrane.  The extracellular region or extracellular loops (ECL) contain the ligand binding site which upon ligand binding, sends the signal across the membrane and triggers a series of specific cellular response.  The flow of the signal from outside to inside of the cell is mediated by the intracellular loops (ICL) of the receptor which are in contact with cellular signal transduction machinery, most notably the G-protein complex (hence the name of the receptor).  Both ECL and ICL are held in place as functional domains by multiple and intricate interactions among the seven highly hydrophobic transmembrane domains inside the membrane bilayer.  Once out of the membrane environment, GPCR proteins can no longer maintain their physiological conformation and therefore lose their functions.

The requirement for a membrane environment to maintain their conformation and function is the main reason why this family of proteins is so notoriously difficult to work with.  Although various technologies have been developed over the years to overcome the intractability of GPCR proteins by, for example, stabilizing the conformation of GPCRs in vitro through protein engineering, they have not made fundamental changes to the landscape of the field so far.

Platform Technology

The Kangti platform technology is a live cells screening system in which GPCRs are imbedded in the membrane of yeast cells and are able to maintain their normal functions in response to their cognate ligands. Upon introduction of a combinatorial antibody library into these cells, the antibody molecules capable of activating or inactivating the signal transduction of the GPCR are isolated.  This screening platform is robust and efficient, and it significantly increases the success rate in the identification of therapeutic antibody products. 

The Kangti’s antibody discovery system also has the ability to isolate antibodies that activate or inactivate the receptor in a G protein specific manner. 

Kangti has filed a patent for this platform.