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TRAC KO TCR-GP100 T cells are an experimental adoptive cell therapy consisting of T cells engineered to express a transgenic T-cell receptor (TCR) specific for the GP100 (PMEL) melanoma antigen. To enhance the specificity and safety of the therapy, the endogenous T-cell receptor alpha constant (TRAC) gene is knocked out using gene-editing technology such as CRISPR/Cas9. This modification prevents the formation of mixed TCR dimers (mispairing between endogenous and transgenic TCR chains) and eliminates the expression of the native TCR complex, thereby reducing the risk of graft-versus-host disease (GvHD) and ensuring that the T cells are redirected solely toward the tumor antigen. This specific construct has been utilized in research at the University of Pennsylvania as a foundational platform to evaluate further genetic modifications, such as CD5 knockout, aimed at improving T-cell activation and persistence in solid tumors like melanoma.
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