Ontorpacept (TTI-621) is a soluble fusion protein that consists of the human SIRPα N-terminal (1-118) linked to the Fc region of human IgG1. The N-terminal (1-118)-fragment of ontorpacept is a binding domain for CD47 which is an inhibitor of phagocytosis by macrophages. Ontorpacept is a CD47-blocking checkpoint inhibitor with antitumor activity.
Ontorpacept (0.001-1000 nmol/L; 2 h) dose-dependently increases macrophage phagocytosis of tumor cells with an average EC50 of 10 nmol/L in primary samples from patients with AML, MDS, multiple myeloma, B-ALL, and T-ALL[1].
Ontorpacept (8 mg/kg; i.p., 3 times a week for 4 weeks) shows antitumor effects in NOD. SCID mice with AML xenografts[1].
References:
[1]. Petrova PS, et al. TTI-621 (SIRPαFc): A CD47-Blocking Innate Immune Checkpoint Inhibitor with Broad Antitumor Activity and Minimal Erythrocyte Binding. Clin Cancer Res. 2017 Feb 15;23(4):1068-1079.