Preclinical double humanized genO-hCD47/hSIRPα mouse model and MC38 cell line expressing human CD47 for efficacy and safety assessment of anti-CD47/SIRPα-targeting therapies

Background

CD47 is overexpressed on many human tumor cells and interacts with its ligand, the signal-regulating protein alpha (SIRPα), a protein expressed on macrophages and dendritic cells, to induce a “don’t eat me” signal. CD47 and its interaction with phagocytes is therefore a promising therapeutic target to treat cancer. Herein, we describe a double humanized genO-hCD47/hSIRPα model for efficacy, safety assessment and biodistribution of human CD47/SIRPα-targeting therapies in immunocompetent mice. The double humanized genO-hCD47/hSIRPα mouse model (genO-hCD47/hSIRPα) was generated by intercrossing genO-hCD47 and genO-hSIRPα mice models whose designs enable expression of all human isoforms at physiological levels.