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10.1371/journal.pone.0149093 http://scihub22266oqcxt.onion/10.1371/journal.pone.0149093 C4784892!4784892!26959227     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26959227&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       PLoS+One 2016 ; 11 (3): ä Nephropedia Template TP {{tp|p=26959227|t=2016. TGN1412 Induces Lymphopenia and Human Cytokine Release in a Humanized Mouse Model |pdf=|usr=}}{{26959227}} gab.com Text TGN1412 Induces Lymphopenia and Human Cytokine Release in a Humanized Mouse Model JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=26959227 #FOAvip Therapeutic monoclonal antibodies (mAbs) such as the superagonistic, CD28-specific antibody TGN1412, or OKT3, an anti-CD3 mAb, can cause severe adverse events including cytokine release syndrome. A predictive model for mAb-mediated adverse effects, for which no previous knowledge on severe adverse events to be expected or on molecular mechanisms underlying is prerequisite, is not available yet. We used a humanized mouse model of human peripheral blood mononuclear cell-reconstituted NOD-RAG1-/-A?-/-HLADQ(tg+ or tg-)IL-2R?c-/- mice to evaluate its predictive value for preclinical testing of mAbs. 2?6 hours after TGN1412 treatment, mice showed a loss of human CD45+ cells from the peripheral blood and loss of only human T cells after OKT3 injection, reminiscent of effects observed in mAb-treated humans. Moreover, upon OKT3 injection we detected selective CD3 downmodulation on T cells, a typical effect of OKT3. Importantly, we detected release of human cytokines in humanized mice upon both OKT3 and TGN1412 application. Finally, humanized mice showed severe signs of illness, a rapid drop of body temperature, and succumbed to antibody application 2?6 hours after administration. Hence, the humanized mouse model used here reproduces several effects and adverse events induced in humans upon application of the therapeutic mAbs OKT3 and TGN1412. Twit Text FOAVip TGN1412 Induces Lymphopenia and Human Cytokine Release in a Humanized Mouse Model ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=26959227 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26959227 #FOAvip English Wikipedia <ref>{{Cite pmid|26959227}}</ref> TGN1412 Induces Lymphopenia and Human Cytokine Release in a Humanized Mouse Model #MMPMID26959227 Weißmüller S; Kronhart S; Kreuz D; Schnierle B; Kalinke U; Kirberg J; Hanschmann KM; Waibler Z PLoS One 2016[]; 11 (3): ä PMID26959227show ga Therapeutic monoclonal antibodies (mAbs) such as the superagonistic, CD28-specific antibody TGN1412, or OKT3, an anti-CD3 mAb, can cause severe adverse events including cytokine release syndrome. A predictive model for mAb-mediated adverse effects, for which no previous knowledge on severe adverse events to be expected or on molecular mechanisms underlying is prerequisite, is not available yet. We used a humanized mouse model of human peripheral blood mononuclear cell-reconstituted NOD-RAG1-/-A?-/-HLADQ(tg+ or tg-)IL-2R?c-/- mice to evaluate its predictive value for preclinical testing of mAbs. 2?6 hours after TGN1412 treatment, mice showed a loss of human CD45+ cells from the peripheral blood and loss of only human T cells after OKT3 injection, reminiscent of effects observed in mAb-treated humans. Moreover, upon OKT3 injection we detected selective CD3 downmodulation on T cells, a typical effect of OKT3. Importantly, we detected release of human cytokines in humanized mice upon both OKT3 and TGN1412 application. Finally, humanized mice showed severe signs of illness, a rapid drop of body temperature, and succumbed to antibody application 2?6 hours after administration. Hence, the humanized mouse model used here reproduces several effects and adverse events induced in humans upon application of the therapeutic mAbs OKT3 and TGN1412. äTGN1412 Induces Lymphopenia and Human Cytokine Release in a Humanized (epmc).pdf DeepDyve Pubget Overpricing