A Synthetic, Yeast-Based Platform for Integrated Discovery and Production of Heavy Chain Antibodies
Kevin Shutz, Adimab LLC
Significant progress in the generation of bispecific and multi-specific antibodies has occurred over the past decade. However, there remain several complex challenges in the construction of the final therapeutic molecule. One key challenge is how to drive efficient cognate HC- LC pairing of each of the component arms. Heavy chain-only antibodies that do not require a light chain may provide an efficient mechanism for facile generation of multi-specific antibodies. Here we describe the design and deployment of a novel, synthetic heavy chain-only antibody platform that allows for efficient isolation and characterization of heavy chain antibodies via an integrated yeast presentation and production platform. The library design utilizes multiple camelid-derived sequence data sets and machine learning approaches to generate a highly developable, synthetic heavy chain-only antibody library. We will discuss the productivity of this library across multiple therapeutically relevant targets, and we will highlight some of our recent efforts using this library to isolate heavy chain antibodies against CD28. The isolated CD28 heavy chain antibodies may provide effective building blocks to generate multi-specific CD28 T-cell engagers
