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

ABSTRACT: Adoptive immunotherapy using TCR gene-modified T-lymphocytes is an attractive strategy for targeting malignancies. However, TCR mispairings between endogenous and introduced TCR chains are a major concern, as they may induce mixed TCRs with unknown specificities and may reduce the expression of therapeutic TCRs. To overcome these problems, we have recently established a novel retroviral siTCR vector encoding small-interfering RNAs (siRNAs) to knockdown endogenous TCR genes for the efficient expression of therapeutic TCRs. In this study, to improve the efficacy of siTCR vectors, we developed 2A peptide-based siTCR vectors that could increase the expression levels of transduced TCRs compared with internal promoter-based siTCR vectors. We also evaluated the efficacy of an siTCR strategy and t

SUBMITTER: Okamoto S 

PROVIDER: S-EPMC3528300 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature