Anti-SIRPα antibody immunotherapy enhances neutrophil and macrophage antitumor activity

Significance Cancer immunotherapy is a promising therapeutic intervention. However, complete and durable responses are only seen in a fraction of patients who have cancer. Although cells of the myeloid lineage frequently infiltrate tumors and limit therapeutic success, currently approved immunotherapies primarily target tumor-infiltrating T and natural killer lymphocytes. The inhibitory receptor signal regulatory protein-α (SIRPα) represents a myeloid-specific immune checkpoint that engages the “don’t eat me” signal CD47. Here, we developed an anti-human SIRPα antibody, KWAR23, which in combination with tumor-opsonizing antibodies, greatly augmented neutrophil and macrophage antitumor activity in vitro and in vivo. Thus, KWAR23 may represent a promising candidate for combination therapies and may achieve durable responses in a greater number of patients with cancer.