title: Human adenovirus-specific γ/δ 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 α/β 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 γ/δ T cells, which are not allo-reactive. TCR-transfected γ/δ T cells secreted low quantities of cytokines after antigen-specific stimulation, which were increased dramatically after co-transfection of CD8α-encoding mRNA. In direct comparison with TCR-transfected α/β T cells, TCR-CD8α-co-transfected γ/δ T cells produced more tumor necrosis factor (TNF), and lysed peptide-loaded target cells as efficiently. Most importantly, TCR-transfected α/β T cells and TCR-CD8α-co-transfected γ/δ T cells efficiently lysed adenovirus-infected target cells. We show here, for the first time, that not only α/β T cells but also γ/δ 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.
authors.affiliation: Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Dörrie
authors.affiliation: Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany; Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Krug
authors.affiliation: Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hofmann
authors.affiliation: Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Müller
authors.affiliation: Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Wellner
authors.affiliation: Department of Immune Modulation at the Dept. of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Knippertz
authors.affiliation: Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schierer
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg, Regensburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Thomas
authors.affiliation: St. Anna Kinderkrebsforschung e.V., Children's Cancer Research Institute, Vienna, Austria.
authors.forename: Elke
authors.initials: E
authors.lastname: Zipperer
authors.affiliation: St. Anna Kinderkrebsforschung e.V., Children's Cancer Research Institute, Vienna, Austria.
authors.forename: Dieter
authors.initials: D
authors.lastname: Printz
authors.affiliation: St. Anna Kinderkrebsforschung e.V., Children's Cancer Research Institute, Vienna, Austria; Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fritsch
authors.affiliation: Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany; Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Gerold
authors.initials: G
authors.lastname: Schuler
authors.affiliation: Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany; Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Schaft
authors.affiliation: St. Anna Kinderkrebsforschung e.V., Children's Cancer Research Institute, Vienna, Austria.
authors.forename: Rene
authors.initials: R
authors.lastname: Geyeregger
mesh_terms: D000257:Adenoviridae Infections / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D000260:Adenoviruses, Human / Q000276:immunology*; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D016827:CD8 Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D018274:Electroporation; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D061251:Primary Cell Culture; D012313:RNA / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: D000956:Antigens, Viral; D016827:CD8 Antigens; C431698:CD8alpha antigen; D016207:Cytokines; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012313:RNA