Abstract
Cancer immunotherapies using gene-engineered T cells comprise adoptive transfer of T-cell receptor (TCR) and chimeric antigen receptor (CAR) gene-transduced T cells. Although CD19-targeting CAR-T cell therapy is the most progressed, wherein B-cell malignancy is treated efficiently, it also induces cytokine release syndrome and neurotoxicity, which frequently leads to serious adverse events. Of note, TCR-T cell therapy has been primarily used to target melanoma, resulting in 30%-50% of tumor responses. In clinical trials that target NY-ESO-1-expressing synovial sarcoma, a high efficacy of 50%-60% has been obtained. To date, no specific clinical efficacy has been reported for epithelial tumors. Serious on-target adverse effects in normal tissues have been reported when using affinity-enhanced TCR of mutated or mouse-derived ones. Furthermore, there are potential risks in using high-affinity TCRs and in targeting tumor antigens that may also be expressed in normal tissues.
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