A Novel Humanized Mouse Model for Preclinical Assessment of Anti-CD47 and Anti-SIRPα Therapeutics

CD47–SIRPα signaling is a critical myeloid checkpoint that enables tumor cells to evade macrophage phagocytosis, representing a promising target for cancer immunotherapy. To enable preclinical evaluation of this pathway, GemPharmatech developed a BALB/c-based double humanized knock-in mouse model (BALB/c-hCD47/hSIRPα) expressing the extracellular domains of human CD47 and SIRPα. Using CT26-hCD47 colorectal and EMT6-hCD47-hClaudin18.2 triple-negative breast cancer models, the anti-CD47 antibody Magrolimab (5F9) induced dose-dependent tumor regression. Additionally, a bispecific anti-SIRPα × anti-Claudin18.2 antibody demonstrated potent anti-tumor efficacy. This fully immunocompetent model provides a valuable platform for evaluating both monoclonal and bispecific antibodies targeting the CD47–SIRPα axis.