Life-extended glycosylated IL-2 promotes Treg induction and suppression of autoimmunity

Aner Ottolenghi, Priyanka Bolel, Rhitajit Sarkar, Yariv Greenshpan, Muhammed Iraqi, Susmita Ghosh, Baisali Bhattacharya, Zoe V. Taylor, Kiran Kundu, Olga Radinsky, Roi Gazit, David Stepensky, Ron N. Apte, Elena Voronov, Angel Porgador

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


IL-2 is the master-regulator cytokine for T cell dependent responses and is crucial for proliferation and survival of T cells. However, IL-2-based treatments remained marginal, in part due to short half-life. Thus, we aimed to extend IL-2 half-life by flanking the IL-2 core with sequences derived from the extensively glycosylated hinge region of the NCR2 receptor. We termed this modified IL-2: “S2A”. Importantly, S2A blood half-life was extended 14-fold compared to the clinical grade IL-2, Proleukin. Low doses inoculation of S2A significantly enhanced induction of Tregs (CD4+ Regulatory T cells) in vivo, as compared to Proleukin, while both S2A and Proleukin induced low levels of CD8+ T cells. In a B16 metastatic melanoma model, S2A treatment was unable to reduce the metastatic capacity of B16 melanoma, while enhancing induction and recruitment of Tregs, compared to Proleukin. Conversely, in two autoimmune models, rheumatoid arthritis and DSS-induced colitis, S2A treatment significantly reduced the progression of disease compared to Proleukin. Our results suggest new avenues for generating long-acting IL-2 for long-standing treatment and a new technique for manipulating short-life proteins for clinical and research uses.

Original languageEnglish
Article number7676
JournalScientific Reports
Issue number1
StatePublished - 1 Dec 2021

ASJC Scopus subject areas

  • General


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