GPCR Drug Discovery | Antibody Discovery
GPCRs are implicated in a wide variety of diseases where antibody therapeutics are currently used such as inflammatory disease, metabolic disease and cancer. Raising antibodies to GPCRs has been problematic due to difficulties in obtaining suitable antigen; hence there has been a limited degree of success with generating anti-GPCR antibodies to date. The use of StaRs permits generation of GPCRs that are sufficiently stable for production and purification of milligram quantities of homogenous, correctly folded material. Using StaRs in a specific pharmacological conformation may allow isolation of antibodies that will selectivity bind to and stabilize specific conformations. This emerging technology has been employed in both in vitro and in vivo approaches using phage display and standard hybridoma methodology. Notably, monoclonal antibodies have been generated by this approach with functional agonist activity, demonstrating the potential of StaRs to generate therapeutic antibodies.
Molecular model of a generic monoclonal antibody targeting a prototypical GPCR (orange) in the cell membrane. Reference. Hutchings, Koglin and Marshall. MABS 2010. Acknowledgements. Dr Andrew Doré and Dr Ben Tehan, Heptares Therapeutics Ltd, UK. |
