Challenge: G protein-coupled receptors (GPCRs) represent attractive biomarkers and therapeutic target classes in cancer research because their aberrant expression and activity are closely correlated with different stages of tumour initiation and progression. The development of small molecule anticancer drugs targeting GPCRs has so far proven to be quite challenging. Thus, there remains a need to identify new approaches to treating cancer with GPCR-targeted drugs.
Solution: One approach investigated in this project was to develop next generation therapeutic antibodies capable of modulating GPCR signaling. Researchers from the University of Sherbrooke are combining their expertise in GPCR signaling, drug discovery and cancer biology, with that of scientists from Immune Biosolutions (IBio), a Québec biotech specializing in the production of chicken antibodies, to generate novel GPCR-directed antibodies, targeting malignant human cancers. Candidate GPCR targets for cancer therapy include the kinin B1 receptor (B1R), mostly involved in triple-negative breast cancer and prostate cancer, and the neurotensin 1 receptor (NTS1R), mostly involved in non-small cell lung cancer and colorectal cancer. IBio’s platform Nebula was considerably improved and enabled the development of two antibodies against B1R that showed diagnostic, but not therapeutic, potential, as well as the development of one antibody against NTS1R that showed antitumoral activities in vitro first and then in vivo, after optimization, in a mouse model.
Achievements/Impact: This project enabled the optimization of the platform as a bona fide drug discovery strategy, now available from IBio for other projects, as well as the development of GPCR-targeted therapeutics. IBio’s optimized platform was actually awarded a large funding for the discovery of SARS-CoV-2 – specific antibodies at the end of the CQDM project, which are now evaluated in a Phase I trial. The optimization of antibodies able to detect B1R-related cancers is promising for early cancer detection, while the optimization of antibodies able to block NTS1R-related cancers in preliminary studies is promising in the fight against these aggressive cancers.
| Principal Investigator: Fernand Gobeil Jr Université de Sherbrooke |
| Co-investigators Philippe Sarret Université de Sherbrooke Fernand-Pierre Gendron Université de Sherbrooke Simon Gaudreau Immune Biosolutions |
| Completed Project |
| $887,685 / 2 years |
| Supported by CQDM through: – MEI |
| And by co-funding partners: – Immune Biosolutions – Société de recherche sur le cancer – Transfertech – Mitacs – Faculté de médecine et sciences de la santé – Centre de recherche CHUS |
