Discovery of a novel human anti-IL-2 antibody that potentiates Regulatory T cells by a structure-based mechanism
| Autor: | Eleonora Trotta, Paul H. Bessette, Stephanie L. Silveria, Lauren K. Ely, Kevin Jude, Charles R. Holst, Anthony Coyle, Christopher K. Garcia, Natasha K. Crellin, Isaac J. Rondon, Jeffrey A. Bluestone |
|---|---|
| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 200:176.4-176.4 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Interleukin-2 (IL-2) has been shown to suppress immune pathologies by preferentially expanding regulatory T cells (Treg). 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 Treg cells. We report the generation of the first 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 encephalitis, and protected mice against xenogeneic Graft-versus-Host-Disease (GvHD). These results suggest that IL-2-F5111.2 may provide a new immunotherapy to treat autoimmune diseases and GvHD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|