Long-term phenotypic, functional and genetic stability of cancer-specific T-cell receptor (TCR) αβ genes transduced to CD8+ T cells

In adoptive T-cell transfer as an intervention for malignant diseases, retroviral transfer of T-cell receptor (TCR) genes derived from CD8+ cytotoxic T-lymphocyte (CTL) clones provides an opportunity to generate a large number of T cells with the same antigen specificity. We cloned the TCR-αβ genes from a human leukocyte antigen (HLA)-A*2402-restricted CTL clone specific for MAGE-A4143–151. The TCR-αβ genes were transduced to 99.2% of non-TCR expressing SupT1, a human T-cell line, and to 12.7–32.6% of polyclonally activated CD8+ T cells by retroviral transduction. As expected, TCR-αβ gene-modified CD8+ T cells showed cytotoxic activity and interferon-γ production in response to peptide-loaded T2-A*2402 and tumor cell lines expressing both MAGE-A4 and HLA-A*2402. A total of 24 clones were established from TCR-αβ gene-transduced peripheral blood mononuclear cells and all clones were functional on a transduced TCR-dependent manner. Four clones were kept in culture over 6 months for analyses in detail. The transduced TCR-αβ genes were stably maintained phenotypically, functionally and genetically. Our results indicate that TCR-transduced αβ T cells by retroviral transduction represent an efficient and promising strategy for adoptive T-cell transfer for long term.