Tissue factor-targeted immunotherapy of melanoma and triple negative breast cancer using a second generation ICON

Background Hu and colleagues have identified tissue factor (TF-the primary initiator of coagulation and a modulator of angiogenesis) as a common yet specific biomarker and therapeutic target on a variety of cancer cells and angiogenic tumor vascular endothelial cells [1-3]. He has co-invented a TF-targeting Immuno-Conjugate agent named ICON that consists of factor VII (1-406 aa, the natural ligand to tissue factor) fused to the Fc region of IgG1 [1, 2, 4, 5]. Intra-lesional ICON therapy of experimental murine melanoma tumors with an adenoviral vector leads to marked growth tumor inhibition with minimal effects on normal tissues [1]. However, ICON has a relatively big molecular weight (210 kDa) (Figure 1) [5]. To reduce its molecular mass, Hu has developed a second generation ICON, named L-ICON, which consists of only the light chain (1-152 aa) of fVII fused to IgG1Fc (Figure 1). This proposal is designed to evaluate the effects of L-ICON immunotherapy