CV1

CV1 is an engineered, high-affinity variant of the N-terminal V-set domain of Signal Regulatory Protein Alpha (SIRPα), developed at Stanford University. It was identified through yeast surface display libraries to bind CD47 with a dissociation constant (Kd) of approximately 11 pM, representing a 50,000-fold increase in affinity compared to wild-type SIRPα. CV1 functions as a potent CD47 antagonist, effectively blocking the "don't eat me" signal transmitted by CD47 on cancer cells to the endogenous SIRPα receptor on macrophages. This blockade neutralizes the inhibitory signal and promotes the phagocytosis of tumor cells, particularly when used in combination with tumor-targeting monoclonal antibodies that provide a pro-phagocytic "eat me" signal. CV1 has served as a critical research tool and the foundational component for clinical-stage CD47-targeted therapies, such as evorpacept (ALX148), which utilizes CV1 domains in a fusion protein format.

Other names

High-affinity SIRPα variantSIRPα CV1Consensus Variant 1