A Novel Humanized Mouse Model for Preclinical Efficacy Evaluation of Anti-CD47/Anti-SIRPα Therapeutics

CD47 enables tumor cells to evade phagocytic clearance by interacting with Signal Regulatory Protein α (SIRPα) expressed on macrophages and dendritic cells. Therapeutics targeting the CD47-SIRPα pathway promote tumor elimination via two primary mechanisms: 1) blockade of the CD47-SIRPα interaction to facilitate macrophage-mediated phagocytosis, and 2) Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). These mechanisms collectively enhance antigen presentation and stimulate adaptive anti-tumor immunity, establishing the CD47-SIRPα axis as a high-priority target in immuno-oncology. To support the translational evaluation of CD47-targeted therapies, GemPharmatech generated a double knock-in mouse strain, BALB/c-hCD47/hSIRPα. This mouse provides a clinically relevant, immunocompetent model for evaluating therapies targeting the CD47-SIRPα axis. It enables comprehensive assessment of efficacy, immune modulation, and safety, thereby addressing key translational challenges in the development of next-generation macrophage checkpoint inhibitors.