抗CD47/SIRPα標的療法の有効性および安全性を評価するための前臨床用二重ヒト化genO-hCD47/hSIRPαマウスモデルおよびヒトCD47を発現するMC38細胞株

背景

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.