Transduction of a Novel HLA-DRB1*04:05-restricted, WT1-specific TCR Gene into Human CD4(+) T Cells Confers Killing Activity Against Human Leukemia Cells

摘要

Background/Aim: Wilms' tumor gene 1 (WT1) product is a pan-tumor-associated antigen. We previously identified WT1 protein-derived promiscuous helper peptide, WT1 (332). Therefore, isolation and characterization of the WT1 (332)-specific T-cell receptors (TCRs) are useful to develop broadly applicable TCR gene-based adoptive immunotherapy. Materials and Methods: A novel HLA-DRB1*04:05-restricted WT1 (332)-specific TCR gene was cloned and transduced into human CD4(+) T-cells by using a lentiviral vector. Results: The WT1(332)-specific TCR-transduced CD4(+) T-cells showed strong proliferation and Th1-cytokine production in an HLA-DRB1*04:05-restricted, WT1 (332)-specific manner. Furthermore, the WT1 (332)-specific TCR-transduced CD4(+) Teens could lyse HLA-DRB1*04:05-positive, WT1-expressing leukemia cells in vitro. Conclusion: The novel TCR gene cloned here should be a promising tool to develop adoptive immunotherapy of WT1 (332)-specific TCR-transduced CD4(+) T-cells for the treatment of WT1-expressing cancer, such as leukemia.