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10.1038/mto.2016.23 http://scihub22266oqcxt.onion/10.1038/mto.2016.23 C5904357!5904357 !29675462     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 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\29675462 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Mol+Ther+Oncolytics 2016 ; 3 (ä): 1-9 Nephropedia Template TP {{tp|p=29675462 |t=2016. An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity |pdf=|usr=}}{{29675462 }} gab.com Text An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity JO: Mol Ther Oncolytics http://www.kidney.de/pget.php?&tw=1&pmid=29675462 #FOAvip Chimeric antigen receptors (CARs) are synthetic receptors that usually redirect T cells to surface antigens independent of human leukocyte antigen (HLA). Here, we investigated a T cell receptor-like CAR based on an antibody that recognizes HLA-A*0201 presenting a peptide epitope derived from the cancer-testis antigen NY-ESO-1. We hypothesized that this CAR would efficiently redirect transduced T cells in an HLA-restricted, antigen-specific manner. However, we found that despite the specificity of the soluble Fab, the same antibody in the form of a CAR caused moderate lysis of HLA-A2 expressing targets independent of antigen owing to T cell avidity. We hypothesized that lowering the affinity of the CAR for HLA-A2 would improve its specificity. We undertook a rational approach of mutating residues that, in the crystal structure, were predicted to stabilize binding to HLA-A2. We found that one mutation (DN) lowered the affinity of the Fab to T cell receptor-range and restored the epitope specificity of the CAR. DN CAR T cells lysed native tumor targets in vitro, and, in a xenogeneic mouse model implanted with two human melanoma lines (A2+/NYESO+ and A2+/NYESO-), DN CAR T cells specifically migrated to, and delayed progression of, only the HLA-A2+/NY-ESO-1+ melanoma. Thus, although maintaining MHC-restricted antigen specificity required T cell receptor-like affinity that decreased potency, there is exciting potential for CARs to expand their repertoire to include a broad range of intracellular antigens. Twit Text FOAVip An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity ????Mol Ther Oncolytics http://www.kidney.de/pget.php?&tw=1&pmid=29675462 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29675462 #FOAvip English Wikipedia <ref>{{Cite pmid|29675462 }}</ref> An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity #MMPMID29675462 Maus MV ; Plotkin J ; Jakka G ; Stewart-Jones G ; Rivière I ; Merghoub T ; Wolchok J ; Renner C ; Sadelain M Mol Ther Oncolytics 2016[]; 3 (ä): 1-9 PMID29675462 show ga Chimeric antigen receptors (CARs) are synthetic receptors that usually redirect T cells to surface antigens independent of human leukocyte antigen (HLA). Here, we investigated a T cell receptor-like CAR based on an antibody that recognizes HLA-A*0201 presenting a peptide epitope derived from the cancer-testis antigen NY-ESO-1. We hypothesized that this CAR would efficiently redirect transduced T cells in an HLA-restricted, antigen-specific manner. However, we found that despite the specificity of the soluble Fab, the same antibody in the form of a CAR caused moderate lysis of HLA-A2 expressing targets independent of antigen owing to T cell avidity. We hypothesized that lowering the affinity of the CAR for HLA-A2 would improve its specificity. We undertook a rational approach of mutating residues that, in the crystal structure, were predicted to stabilize binding to HLA-A2. We found that one mutation (DN) lowered the affinity of the Fab to T cell receptor-range and restored the epitope specificity of the CAR. DN CAR T cells lysed native tumor targets in vitro, and, in a xenogeneic mouse model implanted with two human melanoma lines (A2+/NYESO+ and A2+/NYESO-), DN CAR T cells specifically migrated to, and delayed progression of, only the HLA-A2+/NY-ESO-1+ melanoma. Thus, although maintaining MHC-restricted antigen specificity required T cell receptor-like affinity that decreased potency, there is exciting potential for CARs to expand their repertoire to include a broad range of intracellular antigens. äAn MHC-restricted antibody-based chimeric antigen receptor requires TC(epmc).pdf DeepDyve Pubget Overpricing