Antileukemia multifunctionality of CD4 + T cells genetically engineered by HLA class I-restricted and WT1-specific T-cell receptor gene transfer

摘要: To develop gene-modified T-cell-based antileukemia adoptive immunotherapy, concomitant administration of CD4(+) and CD8(+) T cells that have been gene modified using identical HLA class I-restricted leukemia antigen-specific T-cell receptor (TCR) transfer has not yet fully investigated. Here, had with a retroviral vector expressing HLA-A*24:02-restricted Wilms' tumor 1 (WT1)-specific TCR-α/β genes siRNAs for endogenous TCRs (WT1-siTCR/CD4(+) WT1-siTCR/CD8(+) cells), we examined the utility this strategy. WT1-siTCR/CD4(+) sufficiently recognized in an manner provided target-specific Th1 help cells. By xenografted mouse model, found migrated to sites subsequently attracted via chemotaxis. Therapy-oriented experiments revealed effective enhancement suppression mediated by Importantly, augmented efficacy presence was correlated longer survival enhanced formation memory Collectively, our experimental findings strongly suggest strategy would be clinically advantageous treatment human leukemia.