| http://purl.uniprot.org/citations/26758806 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26758806 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26758806 | http://www.w3.org/2000/01/rdf-schema#comment | "Natural T-cell responses generally lack the potency to eradicate cancer. Enhanced affinity T-cell receptors (TCRs) provide an ideal approach to target cancer cells, with emerging clinical data showing significant promise. Nevertheless, the risk of off target reactivity remains a key concern, as exemplified in a recent clinical report describing fatal cardiac toxicity, following administration of MAGE-A3 specific TCR-engineered T-cells, mediated through cross-reactivity with an unrelated epitope from the Titin protein presented on cardiac tissue. Here, we investigated the structural mechanism enabling TCR cross-recognition of MAGE-A3 and Titin, and applied the resulting data to rationally design mutants with improved antigen discrimination, providing a proof-of-concept strategy for altering the fine specificity of a TCR towards an intended target antigen. This study represents the first example of direct molecular mimicry leading to clinically relevant fatal toxicity, mediated by a modified enhanced affinity TCR designed for cancer immunotherapy. Furthermore, these data demonstrate that self-antigens that are expressed at high levels on healthy tissue should be treated with extreme caution when designing immuno-therapeutics."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.org/dc/terms/identifier | "doi:10.1038/srep18851"xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.org/dc/terms/identifier | "doi:10.1038/srep18851"xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Rizkallah P.J."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Rizkallah P.J."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Cole D.K."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Cole D.K."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Jakobsen B.K."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Jakobsen B.K."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Vuidepot A."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Vuidepot A."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Raman M.C."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Raman M.C."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Mahon T."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Mahon T."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Sami M."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Sami M."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Simmons R."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Simmons R."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Bossi G."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Bossi G."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Baston E."xsd:string |
| http://purl.uniprot.org/citations/26758806 | http://purl.uniprot.org/core/author | "Baston E."xsd:string |