Dickkopf-1 (DKK1) is an endogenous protein known to over-express in tumor micro-environments. Previous studies have shown the anti-tumor effect of anti-DKK1 antibodies in multiple different cancers. Twist Biopharma Solutions’ multidisciplinary gold-standard platform integrates in vitro, in vivo, and in silico approaches for antibody discovery.

In this campaign, we leveraged Twist’s in vitro and in silico approaches, taking advantage of Twist’s high-diversity synthetic phage libraries as well as machine-learning strategies to discover potent anti-DKK1 antibodies. Two synthetic humanized VHH libraries were panned using phage display, and phage panning outputs were screened by ELISA to identify potential candidates. Panning outputs were also sequenced by Next Generation Sequencing (NGS)– NGS outputs were leveraged in various machine learning models to predict additional potential candidates. Sequences were reformatted into VHH-Fc, and synthesized and produced with Twist’s high throughput synthesis and production platform. 

Resulting antibodies were evaluated for binding on SPR, as well as further downstream characterization and in vivo studies. Additionally, our modular VHH platform allowed us to rapidly reformat promising mAbs into bispecific antibodies (bsAb).