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  • Title: A humanized monoclonal antibody against interleukin-2 that can inactivate the cytokine/receptor complex.
    Author: Volkland J, Lumsden J, Mølhøj M, Raum T, Hausmann S, Wissing S, Wissinger M, Hoffmann P, Sriskandarajah M, Kvesic M, Baeuerle PA, Pflanz S.
    Journal: Mol Immunol; 2007 Mar; 44(7):1743-53. PubMed ID: 17000002.
    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 gamma-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 gamma-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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