Zusammenfassung
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 alpha/beta T cells with mRNA encoding a T-cell receptor (TCR) specific for the HLA-A*0101-restricted peptide ...
Zusammenfassung
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 alpha/beta 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 gamma/delta T cells, which are not allo-reactive. TCR-transfected gamma/delta T cells secreted low quantities of cytokines after antigen-specific stimulation, which were increased dramatically after co-transfection of CD8 alpha-encoding mRNA. In direct comparison with TCR-transfected alpha/beta T cells, TCR-CD8 alpha-co-transfected gamma/delta T cells produced more tumor necrosis factor (TNF), and lysed peptide-loaded target cells as efficiently. Most importantly, TCR-transfected alpha/beta T cells and TCR-CD8 alpha-co-transfected gamma/delta T cells efficiently lysed adenovirus-infected target cells. We show here, for the first time, that not only alpha/beta T cells but also gamma/delta T cells can be equipped with an adenovirus specificity by TCR-RNA electroporation. Thus, our strategy offers a new means for the immunotherapy of adenovirus infection after allogeneic HSCT.
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