Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2833365 | Molecular Immunology | 2007 | 11 Pages |
Abstract
Inhibition of the interleukin-2 (IL-2) pathway has potent immunosuppressive activity in humans as is evident from the broad therapeutic utility of cyclosporine, rapamycin, tacrolimus, and monoclonal antibodies blocking the high-affinity subunit of the IL-2 receptor (CD25). Here we describe a humanized antibody, MT204, interfering with IL-2 signaling by a novel mechanism. Although MT204 did not prevent IL-2 from binding to CD25, it potently antagonized downstream signaling events of IL-2 at sub-nanomolar concentrations, such as STAT3 tyrosine phosphorylation, expression of CD124, production of γ-interferon and cell proliferation. While MT204 and the anti-CD25 mAb daclizumab were equally effective in inhibiting autocrine growth of human CD4+ T cells, MT204 was far superior in preventing proliferation of NKL lymphoma cells, production of γ-interferon by natural killer (NK) cells and proliferation of primary NK cells. MT204 has potential as a novel immunosuppressive and anti-proliferative therapy with an apparently broader spectrum of activities than anti-CD25 antibodies.
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Authors
Jörg Volkland, John Lumsden, Michael Mølhøj, Tobias Raum, Susanne Hausmann, Sandra Wissing, Monika Wissinger, Patrick Hoffmann, Mirnaalini Sriskandarajah, Majk Kvesic, Patrick A. Baeuerle, Stefan Pflanz,