Researchers at the University of Pittsburgh have developed fully human monoclonal antibodies (mAbs) targeting the myeloid-specific immune checkpoint SIRPα, which interacts with CD47 to inhibit macrophage-mediated phagocytosis. These antibodies have shown potential in restoring macrophage-mediated phagocytosis and enhancing anti-tumor responses, offering novel therapeutic avenues for cancer treatment without the side effects associated with targeting CD47 directly. The antibodies were identified through panning of phage-displayed Fab and VH libraries and have demonstrated high specificity and efficacy in blocking the SIRPα-CD47 interaction.
Description
SIRPα is a receptor for CD47, expressed on both tumors and normal tissues, and represents a promising target for cancer immunotherapy. The engagement of CD47 with SIRPα activates an antiphagocytic "don't eat me" signal in macrophages, dendritic cells, and neutrophils. The developed mAbs, including 1B3 Fab and 1A3 VH, have shown high specificity to SIRPα and effectively block its interaction with CD47. These antibodies restore macrophage-mediated phagocytosis when combined with anti-EGFR antibodies, enhancing anti-tumor responses.
Applications
• Therapeutic antibody
• Cancer immunotherapy
• Immune checkpoint inhibitor
Advantages
• High specificity and affinity to SIRPα
• Effective blockade of SIRPα-CD47 interaction
• Potential to restore macrophage-mediated phagocytosis
• Novel therapeutic approach for cancer treatment without side effects
• Fully human antibodies reduce the risk of immunogenicity
Invention Readiness
The antibodies have been developed and tested in vitro, demonstrating high specificity and efficacy in blocking the SIRPα-CD47 interaction and restoring macrophage-mediated phagocytosis. The next steps include further preclinical and clinical evaluations to establish their therapeutic potential.
IP Status
Patent pending
