Life Extended IL-2
The number of protein therapeutics being developed is constantly growing, many of them exhibit a short plasma half-life. Extension of protein’s half-life can improve the dosage regime by reducing the number of administrations and also lower drug dosages. An example of such a protein is the cytokine IL-2 omitted from clinical treatment due to high cytotoxicity. We have developed a half-life extended IL-2 modified to preferentially activate T-Regs that could be injected in low doses that retains efficacy but reduces cytotoxicity.
The technology introduces a proprietary human amino acid sequence(s) that upon conjugation (at the DNA level), is able to enhance the biological half-life of soluble protein drugs while maintaining their biological activity. These sequences are specific human sequences rich in O-glycosylation. The developed modified rhIL-2 chimeric protein (S2A), contains both sequence moieties, which supports prolonged systemic presence. S2A showed extended T1/2 in vivo, compared to clinical grade IL-2 (Proleukin, Novartis Pharma SAS, Rueil-Malmaison, France) (Figure 1). Moreover, in a mouse model of DSS-induced Colitis, the modified rhIL-2 achieved better biological activity than an equivalent dose of Proleukin (Figure 2) as indicated by preferential activation of T-Reg cells shown with long lasting IL-2.
- significantly higher T1/2 and improved biological activity in vivo as compared to clinical grade IL-2 (proleukin)
- Reduced IL-2 cytotoxicity
- IL-2 modified to preferentially activate T-Regs
Two PCT applications were filed on September 22nd 2020 and July 11th, 2017, under the application numbers PCT/IL2020/051029 and PCT/IL2017/050788 accordingly
Co-development or licensing out for further development
Prof. Angel Porgador; NIBN and the Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel.