Cancer Research UK and AstraZeneca’s new antibody maturation technique yields high-affinity Arginase 2 antibody

Provider: Pnas
Type: Link
Title: Extensive sequence and structural evolution of Arginase 2 inhibitory antibodies enabled by an unbiased approach to affinity maturation
Description: We describe an antibody optimization strategy that seeks to overcome the restrictive nature of existing affinity-maturation methods, by rapidly exploring a vast sequence space in an unbiased manner through application of PCR techniques and ribosome display. We exemplified the significance of this method by contrasting the crystal structure of the parent and optimized antibodies bound to Arginase 2, which revealed a striking reorientation of the binding paratope, concurrent with distinct improvements in inhibitory potency and binding properties. The nature and magnitude of the epitope expansion was extraordinary and unlikely to have been produced through conventional affinity-maturation methods. This innovative approach demonstrates broad applicability to the optimization of candidate therapeutic antibodies, even those less amenable to CDRH3 targeting.