A Promising Vector for TCR Gene Therapy: Differential Effect of siRNA, 2A Peptide, and Disulfide Bond on the Introduced TCR Expression

摘要: Adoptive immunotherapy using TCR gene-modified T-lymphocytes is an attractive strategy for targeting malignancies. However, mispairings between endogenous and introduced chains are a major concern, as they may induce mixed TCRs with unknown specificities reduce the expression of therapeutic TCRs. To overcome these problems, we have recently established novel retroviral siTCR vector encoding small-interfering RNAs (siRNAs) to knockdown genes efficient In this study, improve efficacy vectors, developed 2A peptide-based vectors that could increase levels transduced compared internal promoter-based vectors. We also evaluated addition new interchain disulfide bond created by cysteine modification. found effect modification depended on variations, while improved all tested. Furthermore, combined strategies was highly significant certain Therefore, our technology, in isolation or combination another strategy, open door effective cancer patients.