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10.1038/ncomms15373 http://scihub22266oqcxt.onion/10.1038/ncomms15373 C5437307!5437307 !28497796     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28497796 &cmd=llinks): Failed to open stream: HTTP request failed! 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Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc-mediated depletion of regulatory T-cells |pdf=|usr=}}{{28497796 }} gab.com Text Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc-mediated depletion of regulatory T-cells JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=28497796 #FOAvip Interleukin-2 (IL-2) is an established therapeutic agent used for cancer immunotherapy. Since treatment efficacy is mediated by CD8(+) and NK cell activity at the tumour site, considerable efforts have focused on generating variants that expand these subsets systemically, as exemplified by IL-2/antibody complexes and 'superkines'. Here we describe a novel determinant of antitumour activity using fusion proteins consisting of IL-2 and the antibody fragment crystallizable (Fc) region. Generation of long-lived IL-2-Fc variants in which CD25 binding is abolished through mutation effectively prevents unwanted activation of CD25(+) regulatory T-cells (Tregs) and results in strong expansion of CD25(-) cytotoxic subsets. Surprisingly, however, such variants are less effective than wild-type IL-2-Fc in mediating tumour rejection. Instead, we report that efficacy is crucially dependent on depletion of Tregs through Fc-mediated immune effector functions. Our results underpin an unexpected mechanism of action and provide important guidance for the development of next generation IL-2 therapeutics. Twit Text FOAVip Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc-mediated depletion of regulatory T-cells ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=28497796 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28497796 #FOAvip English Wikipedia <ref>{{Cite pmid|28497796 }}</ref> Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc-mediated depletion of regulatory T-cells #MMPMID28497796 Vazquez-Lombardi R ; Loetsch C ; Zinkl D ; Jackson J ; Schofield P ; Deenick EK ; King C ; Phan TG ; Webster KE ; Sprent J ; Christ D Nat Commun 2017[May]; 8 (ä): 15373 PMID28497796 show ga Interleukin-2 (IL-2) is an established therapeutic agent used for cancer immunotherapy. Since treatment efficacy is mediated by CD8(+) and NK cell activity at the tumour site, considerable efforts have focused on generating variants that expand these subsets systemically, as exemplified by IL-2/antibody complexes and 'superkines'. Here we describe a novel determinant of antitumour activity using fusion proteins consisting of IL-2 and the antibody fragment crystallizable (Fc) region. Generation of long-lived IL-2-Fc variants in which CD25 binding is abolished through mutation effectively prevents unwanted activation of CD25(+) regulatory T-cells (Tregs) and results in strong expansion of CD25(-) cytotoxic subsets. Surprisingly, however, such variants are less effective than wild-type IL-2-Fc in mediating tumour rejection. Instead, we report that efficacy is crucially dependent on depletion of Tregs through Fc-mediated immune effector functions. Our results underpin an unexpected mechanism of action and provide important guidance for the development of next generation IL-2 therapeutics. |*Immunotherapy [MESH] |*Lymphocyte Activation [MESH] |Animals [MESH] |Antibodies, Monoclonal/immunology [MESH] |Antineoplastic Agents/*pharmacology [MESH] |CD8-Positive T-Lymphocytes/immunology [MESH] |Cytokines/metabolism [MESH] |Female [MESH] |Immunoglobulin Fragments/*immunology [MESH] |Immunoglobulin G/immunology [MESH] |Immunologic Memory [MESH] |Interleukin-2 Receptor alpha Subunit/metabolism [MESH] |Interleukin-2/pharmacology [MESH] |Killer Cells, Natural/immunology [MESH] |Leukocytes, Mononuclear/cytology [MESH] |Lymphocyte Subsets/immunology [MESH] |Melanoma, Experimental [MESH] |Mice [MESH] |Mice, Inbred BALB C [MESH] |Mice, Inbred C57BL [MESH] |Mutagenesis [MESH] |Neoplasms/*immunology/therapy [MESH] |Recombinant Proteins/metabolism [MESH] |Spleen/cytology/metabolism [MESH]Potent antitumour activity of interleukin-2-Fc fusion proteins require(epmc).pdf DeepDyve Pubget Overpricing