Application of Adoptive T-Cell Therapy Using Tumor Antigen-Specific T-Cell Receptor Gene Transfer for the Treatment of Human Leukemia
Reported modifications of TSA/TAA-specific TCR transduction. With the aim of enhancing the surface expression level of the transduced TCR heterodimer, modifications are largely categorized into two options. One is to modify the target-TCR gene itself, and the other is to transduce alternative cells other than normal peripheral T lymphocytes. The former involves the murine/human hybrid, a modified two-chain TCR that encompasses total human CD3, additional disulfide-bond insertion, codon modification, and insertion of built-in silencers for endogenous TCR. The latter involves TCR transduction into T cells. These options aim to enhance the immediate antitumor effect of transfectants. On the other hand, TCR-gene transduction into hematopoietic stem cells is particularly aimed at achieving the prolonged presence of transfectants, which will be able to provide a durable antitumor effect.
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