Multi-specific antibody-like molecules capable of blocking several receptor signaling pathways and recruiting adaptive immune functions represent a promising new class of anti-cancer agents. Yet, their construction has faced significant challenges due to the large number of interlinked optimization parameters, such as multiple affinities, avidities and CMC properties. To solve this problem we have developed an integrated approach that combines systems biology-driven design to reveal optimal inhibitor characteristics and to identify independent engineering modules with rapid antibody optimization platform. We implemented focused yeast display selection protocols to  optimize antibody modules for high affinity and robust pharmaceutical properties in a single campaign. We showed that these modules retain their optimal properties both as soluble proteins and as components of multi-specific antibody-like molecules.  Here, we present an application of this approach to optimization of a bispecific molecule targeting two receptor tyrosine kinases.

Rapid optimization of antibody modules  to enable construction of multi-specific antibody therapeutics.

243rd National Meeting (2012)

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