A humanized monoclonal antibody against interleukin-2 that can inactivate the cytokine/receptor complex

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 humaniz...

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Veröffentlicht in:Molecular Immunology 2007-03, Vol.44 (7), p.1743-1753
Hauptverfasser: Volkland, Jörg, Lumsden, John, Mølhøj, Michael, Raum, Tobias, Hausmann, Susanne, Wissing, Sandra, Wissinger, Monika, Hoffmann, Patrick, Sriskandarajah, Mirnaalini, Kvesic, Majk, Baeuerle, Patrick A., Pflanz, Stefan
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Sprache:eng
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Zusammenfassung: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.
ISSN:0161-5890
1872-9142
1365-2567
DOI:10.1016/j.molimm.2006.07.296