ALOS4: A Novel Cyclic Peptide with Anti-Cancer and Anti-Inflammatory Properties

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.

Principal Investigators: Prof. Albert Pinhasov, Dr. Elemeleh Nesher

The Tumor Cells Biology Lab

This research was published in a scientific journals:

Debpali Sur , Katerina Leonova , Bar Levi , Shany Ivon Markowitz, Raichel Cohen-Harazi , Ilya Gitlin , Katerina Gurova , Andrei Gudkov , Albert Pinhasov , Igor Koman , Elimelech Nesher ,Targeted Modulation of Interferon Response-Related Genes with IFN-Alpha/Lambda Inhibition, Int. Journal of Molecular Science, 2022 Jun 29;23(13):7248

https://pubmed.ncbi.nlm.nih.gov/35806255/

Bar Levi , Shiri Yacobovich , Michael Kirby , Maria Becker , Oryan Agranyoni , Boris Redko , Gary Gellerman , Albert Pinhasov,  Igor Koman, Elimelech Nesher  ,Anti-Cancer Effects of Cyclic Peptide ALOS4 in a Human Melanoma Mouse Model, Int. Journal of Molecular Science, 2021 Sep 3;22(17):9579.

https://pubmed.ncbi.nlm.nih.gov/34502483/

Shiri Yacobovich, Lena Tuchinsky , Michael Kirby , Tetiana Kardash , Oryan Agranyoni , Elimelech Nesher , Boris Redko , Gary Gellerman, Dror Tobi , Katerina Gurova , Igor Koman, Osnat Ashur Fabian , Albert Pinhasov , Novel synthetic cyclic integrin αvβ3 binding peptide ALOS4: Antitumor activity in mouse melanoma models, Oncotarget, 2016 Sep 27;7(39):63549-63560

https://pubmed.ncbi.nlm.nih.gov/27556860/