| Literature DB >> 33828163 |
Aner Ottolenghi1,2, Priyanka Bolel1,2, Rhitajit Sarkar1, Yariv Greenshpan1,2, Muhammed Iraqi1,2, Susmita Ghosh1,2, Baisali Bhattacharya1, Zoe V Taylor1, Kiran Kundu1,2, Olga Radinsky1, Roi Gazit1,2, David Stepensky3, Ron N Apte1, Elena Voronov1, Angel Porgador4,5.
Abstract
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.Entities:
Year: 2021 PMID： 33828163 DOI： 10.1038/s41598-021-87102-4
Source DB: PubMed Journal: Sci Rep ISSN： 2045-2322 Impact factor: 4.379