CD47-SIRPα-targeted therapeutics: status and prospects

CD47 is a "don't eat me" signal to phagocytes that is overexpressed on many tumor cells as a potential mechanism for immune surveillance evasion. CD47 and its interaction with signal-regulating protein alpha (SIRPα) on phagocytes is therefore a promising cancer target. Therapeutic antibodies and fusion proteins that block CD47 or SIRPα have been developed and have shown activity in preclinical models of hematologic and solid tumors. Anemia is a common adverse event associated with anti-CD47 treatment, but mitigation strategies-including use of a low 'priming' dose-have substantially reduced this risk in clinical studies. While efficacy in single-agent clinical studies is lacking, findings from studies of CD47-SIRPα blockade in combination with agents that increase 'eat me' signals or with antitumor antibodies are promising. Magrolimab, an anti-CD47 antibody, is the furthest along in clinical development among agents in this class. Magrolimab combination therapy in phase Ib/II studies has been well tolerated with encouraging response rates in hematologic and solid malignancies. Similar combination therapy studies with other anti-CD47-SIRPα agents are beginning to report. Based on these early clinical successes, many trials have been initiated in hematologic and solid tumors testing combinations of CD47-SIRPα blockade with standard therapies. The results of these studies will help determine the role of this novel approach in clinical practice and are eagerly awaited.