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10.1371/journal.pone.0162472 http://scihub22266oqcxt.onion/10.1371/journal.pone.0162472 C5017640!5017640 !27611189     free     free     free 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 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 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27611189 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       PLoS+One 2016 ; 11 (9 ): e0162472 Nephropedia Template TP {{tp|p=27611189 |t=2016. Targeting Attenuated Interferon-? to Myeloma Cells with a CD38 Antibody Induces Potent Tumor Regression with Reduced Off-Target Activity |pdf=|usr=}}{{27611189 }} gab.com Text Targeting Attenuated Interferon- to Myeloma Cells with a CD38 Antibody Induces Potent Tumor Regression with Reduced Off-Target Activity JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=27611189 #FOAvip Interferon-? (IFN?) has been prescribed to effectively treat multiple myeloma (MM) and other malignancies for decades. Its use has waned in recent years, however, due to significant toxicity and a narrow therapeutic index (TI). We sought to improve IFN?'s TI by, first, attaching it to an anti-CD38 antibody, thereby directly targeting it to MM cells, and, second, by introducing an attenuating mutation into the IFN? portion of the fusion protein rendering it relatively inactive on normal, CD38 negative cells. This anti-CD38-IFN?(attenuated) immunocytokine, or CD38-Attenukine?, exhibits 10,000-fold increased specificity for CD38 positive cells in vitro compared to native IFN? and, significantly, is ~6,000-fold less toxic to normal bone marrow cells in vitro than native IFN?. Moreover, the attenuating mutation significantly decreases IFN? biomarker activity in cynomolgus macaques indicating that this approach may yield a better safety profile in humans than native IFN? or a non-attenuated IFN? immunocytokine. In human xenograft MM tumor models, anti-CD38-IFN?(attenuated) exerts potent anti-tumor activity in mice, inducing complete tumor regression in most cases. Furthermore, anti-CD38-IFN?(attenuated) is more efficacious than standard MM treatments (lenalidomide, bortezomib, dexamethasone) and exhibits strong synergy with lenalidomide and with bortezomib in xenograft models. Our findings suggest that tumor-targeted attenuated cytokines such as IFN? can promote robust tumor killing while minimizing systemic toxicity. Twit Text FOAVip Targeting Attenuated Interferon- to Myeloma Cells with a CD38 Antibody Induces Potent Tumor Regression with Reduced Off-Target Activity ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=27611189 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27611189 #FOAvip English Wikipedia <ref>{{Cite pmid|27611189 }}</ref> Targeting Attenuated Interferon-? to Myeloma Cells with a CD38 Antibody Induces Potent Tumor Regression with Reduced Off-Target Activity #MMPMID27611189 Pogue SL ; Taura T ; Bi M ; Yun Y ; Sho A ; Mikesell G ; Behrens C ; Sokolovsky M ; Hallak H ; Rosenstock M ; Sanchez E ; Chen H ; Berenson J ; Doyle A ; Nock S ; Wilson DS PLoS One 2016[]; 11 (9 ): e0162472 PMID27611189 show ga Interferon-? (IFN?) has been prescribed to effectively treat multiple myeloma (MM) and other malignancies for decades. Its use has waned in recent years, however, due to significant toxicity and a narrow therapeutic index (TI). We sought to improve IFN?'s TI by, first, attaching it to an anti-CD38 antibody, thereby directly targeting it to MM cells, and, second, by introducing an attenuating mutation into the IFN? portion of the fusion protein rendering it relatively inactive on normal, CD38 negative cells. This anti-CD38-IFN?(attenuated) immunocytokine, or CD38-Attenukine?, exhibits 10,000-fold increased specificity for CD38 positive cells in vitro compared to native IFN? and, significantly, is ~6,000-fold less toxic to normal bone marrow cells in vitro than native IFN?. Moreover, the attenuating mutation significantly decreases IFN? biomarker activity in cynomolgus macaques indicating that this approach may yield a better safety profile in humans than native IFN? or a non-attenuated IFN? immunocytokine. In human xenograft MM tumor models, anti-CD38-IFN?(attenuated) exerts potent anti-tumor activity in mice, inducing complete tumor regression in most cases. Furthermore, anti-CD38-IFN?(attenuated) is more efficacious than standard MM treatments (lenalidomide, bortezomib, dexamethasone) and exhibits strong synergy with lenalidomide and with bortezomib in xenograft models. Our findings suggest that tumor-targeted attenuated cytokines such as IFN? can promote robust tumor killing while minimizing systemic toxicity. |ADP-ribosyl Cyclase 1/*metabolism [MESH] |Animals [MESH] |Cell Survival/drug effects [MESH] |Cells, Cultured [MESH] |Flow Cytometry [MESH] |Humans [MESH] |Interferon-alpha/*pharmacology/therapeutic use [MESH] |Macaca fascicularis [MESH] |Multiple Myeloma/drug therapy/*metabolism [MESH] |Mutation/genetics [MESH] |Receptor, Interferon alpha-beta/genetics/metabolism [MESH]Targeting Attenuated Interferon-? to Myeloma Cells with a CD38 Antibod(epmc).pdf DeepDyve Pubget Overpricing