Human Adenovirus-Specific c/d and CD8+ T Cells Generated by T-Cell Receptor Transfection to Treat Adenovirus Infection after Allogeneic Stem Cell

Human adenovirus infection is life threatening after allogeneic haematopoietic stem cell transplantation (HSCT). Immunotherapy with donor-derived adenovirus-specific T cells is promising; however, 20 % of all donors lack adenovirus-specific T cells. To overcome this, we transfected a/b T cells with mRNA encoding a T-cell receptor (TCR) specific for the HLA-A*0101-restricted peptide LTDLGQNLLY from the adenovirus hexon protein. Furthermore, since allo-reactive endogenous TCR of donor T lymphocytes would induce graft-versus-host disease (GvHD) in a mismatched patient, we transferred the TCR into c/d T cells, which are not allo-reactive. TCR-transfected c/d T cells secreted low quantities of cytokines after antigen-specific stimulation, which were increased dramatically after co-transfection of CD8a-encoding mRNA. In direct comparison with TCR-transfected a/b T cells, TCR-CD8a-co-transfected c/d T cells produced more tumor necrosis factor (TNF), and lysed peptide-loaded target cells as efficiently. Most importantly, TCR-transfected a/b T cells and TCR-CD8a-co-transfected c/d T cells efficiently lysed adenovirus-infected target cells. We show here, for the first time, that not only a/b T cells but also c/d T cells can be equipped with an adenovirus specificity by TCR-RNA electroporation. Thus, our strateg