biostudies-literatureUnknown13Li W<h4>Introduction</h4>The major challenge for universal chimeric antigen receptor T cell (UCAR-T) therapy is the inability to persist for a long time in patients leading to inferior efficacy clinically. The objective of this study was to design a novel UCAR-T cell that could avoid the occurrence of allo-rejection and provide effective resistance to allogeneic Natural Killer (NK) cell rejection, together with the validation of its safety and efficacy <i>ex vivo</i> and <i>in vivo</i>.<h4>Methods</h4>We prepared T-cell receptor (TCR), Human leukocyte antigen (HLA)-I/II triple-edited (TUCAR-T) cells and evaluated the anti-tumor efficacy ex vivo and in vivo. We measured the resistance of exogenous HLA-E expressing TUCAR-T (ETUCAR-T) to NK rejection by using an enhanced NK. Furthermore, we estabFrontiers in immunology1052717https://www.ebi.ac.uk/biostudies/studies/S-EPMC9757162biostudies-literatureSimultaneous editing of TCR, HLA-I/II and HLA-E resulted in enhanced universal CAR-T resistance to allo-rejection.PMC9757162Li WYang ZLi YShen JChen JQian CHong JZhang HQi YZhu XWang GXu YfalseSimultaneous editing of TCR, HLA-I/II and HLA-E resulted in enhanced universal CAR-T resistance to allo-rejection.<h4>Introduction</h4>The major challenge for universal chimeric antigen receptor T cell (UCAR-T) therapy is the inability to persist for a long time in patients leading to inferior efficacy clinically. The objective of this study was to design a novel UCAR-T cell that could avoid the occurrence of allo-rejection and provide effective resistance to allogeneic Natural Killer (NK) cell rejection, together with the validation of its safety and efficacy <i>ex vivo</i> and <i>in vivo</i>.<h4>Methods</h4>We prepared T-cell receptor (TCR), Human leukocyte antigen (HLA)-I/II triple-edited (TUCAR-T) cells and evaluated the anti-tumor efficacy ex vivo and in vivo. We measured the resistance of exogenous HLA-E expressing TUCAR-T (ETUCAR-T) to NK rejection by using an enhanced NK. Furthermore, we estab2022-01-01T00:00:00Z20222026-06-18T07:44:44.222Z2024-11-10T03:44:46.924ZS-EPMC97571623653200610.3389/fimmu.2022.1052717