Human adenovirus-specific ?/? and CD8+ T cells generated by T-cell receptor transfection to treat adenovirus infection after allogeneic stem cell transplantation.

ABSTRACT: 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 ?/? 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 ?/? T cells, which are not allo-reactive. TCR-transfected ?/? T cells secreted low quantities of cytokines after antigen-specific stimulation, which were increased dramatically after co-transfection of CD8?-encoding mRNA. In direct comparison with TCR-transfected ?/? T cells, TCR-CD8?-co-transfected ?/? T cells produced more tumor necrosis factor (TNF), and lysed peptide-loaded target cells as efficiently. Most importantly, TCR-transfected ?/? T cells and TCR-CD8?-co-transfected ?/? T cells efficiently lysed adenovirus-infected target cells. We show here, for the first time, that not only ?/? T cells but also ?/? 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.

SUBMITTER: Dorrie J 

PROVIDER: S-EPMC4188623 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature