As part of its pre-clinical development, the KAHR-101 protein was shown to exhibit high activity in multiple animal disease models for cancer and autoimmune diseases.
KAHR-101 is a fusion-protein that links portions of two membrane proteins - Fn14 and TRAIL, both implicated in immunity and cancer.
Fn14 is the receptor for TWEAK – an important pro-inflammatory cytokine and growth factor that controls many cellular activities and physiological processes; the TWEAK–Fn14 axis plays important roles in chronic autoimmune diseases and cancer tumor growth.
TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is an apoptosis-inducing cell surface protein that can be found on specific cell types as well as in a soluble form. TRAIL receptors can be found on activated T-cells and cancer cells and their activation by TRAIL mediates programmed cell death (apoptosis).
Mode of action –
Cell that express TWEAK and TRAIL-receptors, such as activated immune-cells and selected cancer cells, are likely targets for KAHR-101 therapy.
KAHR-101 works by binding TWEAK at disease locations, inhibiting cell growth and inflammatory processes. The binding of TWEAK leads to the formation of localized KAHR-101 clusters that induce highly-active TRAIL-based apoptosis of activated immune-cells or cancer cells.
R&D Status -
The therapeutic activity of KAHR-101 in an animal model of Multiple Sclerosis (MS), has been published in several papers (see; Razmara et-al, 2009, Am. J. Pathol.; Prinz-Hadad et-al. 2013, Journal of Neuroinflammation; Aronin, et-al. PLOS ONE, 2013) and have shown treatment activity in animal disease models for Liver cancer (HCC), Renal cancer (RCC) and Rheumatoid Arthritis (RA).