The right binder, delivered to the right immune cell
Harbour Mice® transgenic mice platforms (H2L2 and HCAb) enable the generation of fully human antibodies with excellent developability for therapeutic applications. Additionally, in certain scenarios, protein engineering is required to modify molecules to acquire new properties or create innovative modalities.
Our scientific team has accumulated extensive experience in protein engineering and commits to use state-of-the-art techniques to deliver the best biologics. We leverage powerful surface display technologies to capture millions of molecular variants and employ structural biology and molecular dynamics to capture atomic changes.
We have established both phage display and yeast display technology platforms to meet various applications of directed evolution for protein engineering. These platforms facilitate the discovery of antibodies from immunized animals, human PBMCs or other sources , and facilitate tasks such as affinity maturation, PTM removal, cross-reactivity optimization, and improvement of biophysical properties.
Both phage display and yeast display technologies are suitable for multiple different applications, however, each technology has its own advantages in specific scenarios. Our scientific team selects the most suitable technology based on the nature of the molecule.
Affinity maturation stands as a crucial and widely employed application of surface display technologies in the field of antibody engineering. By combining yeast display technology with streamlined processes for FACS sorting and antibody screening, the workflow of affinity maturation has been significantly shortened, enabling the rapid generation of candidates with enhanced binding activities.
The figure below illustrates the workflow for improving the binding affinity of an HCAb molecule using the yeast display technology platform. Using an anti-PD-1 HCAb as an example,the monomeric VH domain with proper tags (e.g., His-tag) was displayed on the yeast cell surface. Mutagenic libraries were created for each CDR region using degenerated primers, which covered the potential antigen binding sites within the three CDRs. These libraries were subject to MACS sorting and sequential multiple rounds of FACS sorting by proper forms of antigens to isolate the population of yeast cells with increased binding activities. After analyzing the VH sequences of the variants from different mutagenic libraries, the “hotspot” mutations which make critical impacts on antigen binding were identified. The binding activities of the variants from each CDR mutagenic library can be ranked by FACS or Octet. The “hotspot” mutations from each CDR were then combined into a new mutagenic library to include the combinatorial mutagenesis across different CDRs. The new library was subjected to new round of FACS sorting and screening, and the new variants carrying multiple mutations with significantly increased binding activities can be retrieved.
