Leukocyte surface antigen CD47 and B-lymphocyte antigen CD20 (CD47 + CD20)

The dual targeting of Leukocyte surface antigen CD47 and B-lymphocyte antigen CD20 is a therapeutic strategy designed to enhance the immune-mediated clearance of B-cell malignancies. CD47 is a transmembrane protein that acts as an immune checkpoint by sending a "don't eat me" signal to macrophages through its interaction with SIRPα, thereby preventing phagocytosis of both healthy and malignant cells [3, 4]. CD20 is a well-characterized B-cell surface marker that is highly expressed in most non-Hodgkin lymphomas and is the target of established therapies like rituximab [11, 18]. By co-targeting these molecules, bispecific antibodies or combination therapies can simultaneously block the inhibitory CD47-SIRPα axis and provide a potent pro-phagocytic stimulus via CD20-mediated effector functions [1, 14]. This dual approach aims to improve therapeutic efficacy while minimizing the hematologic toxicities, such as anemia, often associated with monospecific CD47 inhibitors that bind to the large "antigen sink" on red blood cells [9, 19]. Clinical and preclinical developments, such as IMM0306 and CC-96673, utilize affinity-tuning to prioritize binding to CD20-positive tumor cells, thereby focusing the CD47 blockade on the intended target [7, 11].

Other names

CD47CD20Integrin-associated protein (IAP)Membrane-spanning 4-domains subfamily A member 1 (MS4A1)B-lymphocyte surface antigen B1MER6OA3Bp35

Simultaneous blockade of the CD47-SIRPα "don't eat me" inhibitory signal and engagement of CD20 to induce pro-phagocytic signals and effector functions such as antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC).