ALOS4: Evaluation of the anti-inflammatory properties of a Targeted modulation of IFN response-related genes with INF-α/λ inhibition
THE INNOVATION Using a phage–display technique we discovered a 9-amino acid cyclic
peptide named ALOS4 exerting strong anti-cancer properties in vivo and in vitro. Namely, animals with subcutaneous melanoma treated with ALOS4 demonstrated an inhibition of tumor growth and disease progression without any toxicity. While further studying the role of ALOS4 in interferon regulation in malignancy, we found that ALOS4 treatment leads to a decrease of pro-inflammatory cytokines. ALOS4 anti-inflammatory properties are also supported by downregulation of most pro-inflammatory interleukins in the serum of mice subjected to chronic stress and treated with ALOS4. Furthermore, ALOS4 downregulated macrophage quantity in the adipose tissue of these mice and inhibited murine macrophage differentiation to proinflammatory M1 in vitro. Using a cell culture system in which synthetic double stranded RNA (dsRNA) and/or LPS simulates the effects of acute infection, we demonstrated that treatment with ALOS4 leads to a dramatic reduction in expression of interferon response genes and nitric oxide
(NO) production, further supporting its anti-inflammatory properties.
MARKET OPPORTUNITY ALOS4 administration may be considered as an effective measure to manage inflammation of different origin.
✓ Shows No toxicity.
✓ Downregulates cytokines.
✓ Inhibits IFN alpha/lambda upregulation under dsRNA viral mimetic (Poly I:C) treatment,
✓ Does not prevent IFN signaling, but rather supports antiviral response by upregulating IFIT3 expression in an interferon-independent manner.
✓ Downregulates Nitric Oxid levels and macrophage differentiation to pro-inflammatory in murine macrophages in vitro.
✓ Prolongs the lifespan of mice with acute systemic inflammation induced by irradiation.
PRINCIPAL INVESTIGATORS Prof. Albert Pinhasov, Dr. Igor Koman and Dr. Elimelech Nesher are share equal part in the patent. Dr. Nesher a member of Department of Molecular Biology at Ariel University is responsible for the wet lab analysis.