5utz
Human IL-2/Fab complex
Structural highlights
FunctionPublication Abstract from PubMedInterleukin-2 (IL-2) has been shown to suppress immune pathologies by preferentially expanding regulatory T cells (Tregs). However, this therapy has been limited by off-target complications due to pathogenic cell expansion. Recent efforts have been focused on developing a more selective IL-2. It is well documented that certain anti-mouse IL-2 antibodies induce conformational changes that result in selective targeting of Tregs. We report the generation of a fully human anti-IL-2 antibody, F5111.2, that stabilizes IL-2 in a conformation that results in the preferential STAT5 phosphorylation of Tregs in vitro and selective expansion of Tregs in vivo. When complexed with human IL-2, F5111.2 induced remission of type 1 diabetes in the NOD mouse model, reduced disease severity in a model of experimental autoimmune encephalomyelitis and protected mice against xenogeneic graft-versus-host disease. These results suggest that IL-2-F5111.2 may provide an immunotherapy to treat autoimmune diseases and graft-versus-host disease. A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism.,Trotta E, Bessette PH, Silveria SL, Ely LK, Jude KM, Le DT, Holst CR, Coyle A, Potempa M, Lanier LL, Garcia KC, Crellin NK, Rondon IJ, Bluestone JA Nat Med. 2018 Jul;24(7):1005-1014. doi: 10.1038/s41591-018-0070-2. Epub 2018 Jun , 25. PMID:29942088[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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