IGN004 is an antibody-interferon-alpha fusion protein against a novel tumor-associated antigen with both direct anti-tumor and immunostimulatory effects

Results IGN004 unfused antibody bound to the majority of tumor cell lines and primary tumors assessed. Against tumor antigen-positive cells in anti-proliferation experiments, IGN004 demonstrated enhanced potency compared to unfused IFNa while reduced potency was observed in cells lacking antigen expression. IGN004 treatment upregulated MHC class I, PD-L1, and OX-40L on tumor cells. In an in vitro T cell killing assay using TALL-104 cells as effectors and A549 NSCLC cells as targets, the addition of IGN004 led to enhanced effector cell killing of tumor (69.2% killing without IGN004 vs. 100% killing with IGN004; p = 0.001). Importantly, IGN004 demonstrated robust in vivo efficacy against MM, NSCLC, AML, and melanoma xenografts, including patient-derived xenografts (PDX). Against U266 MM xenografts, IGN004 fusion protein caused complete regression of all tumors and achieved long-term survival in 62.5% of mice. Efficacy was tested against a panel of 14 NSCLC PDX tumors and IGN004 had a response rate of 64%, including tumor regression in 29%. In an AML PDX model, IGN004 treatment caused a reduction in AML cells in the blood, spleen and bone marrow. Against a PDX model of melanoma, IGN004 unfused antibody was ineffective while IGN004 fusion protein inhibited tumor growth.