Challenge: G-protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and represent an important class of targets that could be modulated by antibody (Ab)-based therapeutics. However, finding function-modifying antibodies against GPCRs remains a challenge due to the difficulty of preparing purified antigens, poor immunogenicity, small extracellular loops and low expression levels on cells.
Solution: The team has developed an end-to-end platform for the generation of function-modifying antibodies against membrane targets. The platform includes (i) novel single-cell functional assays, (ii) optimized immunization strategies, (iii) instrumentation and microfluidic device improvements to support functional assays and to screen millions of single B cells per campaign, (iv) associated bioinformatics methods, including repertoire sequencing and (v) high-throughput methods for rapid antibody cloning and expression to assess additional function. This new technology preserves the superior properties of natural antibodies while achieving unprecedented throughput and assay versatility that is required for discovery against difficult membrane protein targets. As a proof-of-concept, new lead antibodies against a high-profile GPCR target with high homology against the host proteins (> 95%) were generated and characterized using this technology.
Achievements/Impact: In addition to technology development, a large panel of antibodies against the target was generated, of which a subset demonstrated antagonist and/or antibody inverse agonist activity. Lead monoclonal antibodies discovered through this project may be acquired by participating members for further development as potential therapeutics. Translation and dissemination of this technology will be through AbCellera as an extension of its ongoing partnership business, allowing pharmaceutical and biotechnology companies to access an enabling technology that is needed to accelerate the development of the next generation of antibody therapeutics.
| Principal Investigator: Carl Hansen University of British Columbia |
| Co-Investigators : Véronique Lecault, Kevin Heyries AbCellera Biologics Inc. |
| Completed Project |
| $ 1,000,000 / 1 year |
| Supported by CQDM through: – GSK – Janssen – Merck – Pfizer – Sanofi |
| And by co-founding partner: – Brain Canada Foundation – AbCellera Biologics Inc. |
