Utilizing the AbNano™ VHH Naïve Library for identifying and characterizing VHH binders to key immuno-oncology targets

Amber D. Miller, PhD, Qiang Chen, Jessica Tracy, PhD, Kathy Henze, Fiona H.Y. Yuen, Liz Wilson, Kallie Kilchrist, Nathan Lee, Monique N. Navarro, Andrea Ceron, Michael Spencer, PhD and Sam Sugerman, PhD

VHH domains, derived from the variable heavy chain of the heavy chain-only IgG2 and IgG3 domains in camelids, represent a small, single-domain antibody fragment. Discovering novel VHH domains can take place by multiple workflows, including using B-cell sorting and using display libraries. Within display libraries, the library is generally one of three classes of molecule: synthetic molecules, immune-derived molecules, or naïve germline molecules.
 
Here, we present the construction and early validation of a large naïve library from llamas and alpacas. Characterization data suggests that this library, the AbNanoTM VHH Naïve Library, may be well-suited for rapid discovery of VHH domains binding to therapeutic targets with varying levels of affinity. In this study we show how the AbNano VHH Naïve Library can be used to identify target specific VHHs to PD-L1, including live cell binding by flow cytometry, while reducing the time and resources necessary to do so.