title: Herpes simplex virus type 1 (HSV-1) specific T-cell generation from HLA-A1- and HLA-A2-positive donors for adoptive immunotherapy.
abstract: Herpes simplex virus (HSV) reactivation and infection is common in patients undergoing hematopoietic stem cell transplant (HSCT) and requires routine antiviral prophylaxis. Drug-resistant strains are increasingly common, and effective alternative therapy is currently unavailable. We generated and characterized HSV-1-specific T cells for use in adoptive cellular immunotherapy following allogeneic stem cell transplantation.
  
  
  
  Peripheral blood mononuclear cells from HLA-A1 and HLA-A2 HSV-seropositive hereditary hemochromatosis donors were used as the antigen source. Three HLA-A1 and four HLA-A2 specific epitopes were used for stimulation of T cells. Cells were stimulated with antigen-pulsed dendritic cells and cultured for 21 days in medium with interleukin (IL)-2. Cultured cells were phenotyped and tested for cytokine production, proliferation and cytotoxicity.
  
  
  
  There was a 5.3-fold expansion in total cell numbers over 21 days of culture, with 35% of T cells being CD8 positive. Thirty-five percent, 21% and 5% of CD8 cells secreted interferon-γ, tumor necrosis factor-α and IL-2 upon HSV antigen re-stimulation. More than 50% of antigen-specific T cells secreted multiple cytokines. Cultured T cells proliferated upon antigen re-stimulation and lysed HSV-1 peptide and virus-infected targets.
  
  
  
  It is feasible to generate functional HSV-1 specific T cells from the blood of HLA-A1 and HLA-A2 HSV-seropositive donors using specific peptides. The utility of these cells in preventing and treating HSV-1 reactivation in allogeneic HSCT will need to be tested clinically.
authors: The Westmead Institute for Medical Research, Australia; Blood and Marrow Transplant Unit, Australia.
authors: Chun K K
authors: CK
authors: Ma
authors: The Westmead Institute for Medical Research, Australia; Blood and Marrow Transplant Unit, Australia; Sydney Cell and Gene Therapy Laboratory, Westmead Hospital, The University of Sydney, Sydney, Australia.
authors: Leighton
authors: L
authors: Clancy
authors: The Westmead Institute for Medical Research, Australia; Blood and Marrow Transplant Unit, Australia.
authors: Shivashni
authors: S
authors: Deo
authors: The Westmead Institute for Medical Research, Australia; Blood and Marrow Transplant Unit, Australia; Sydney Cell and Gene Therapy Laboratory, Westmead Hospital, The University of Sydney, Sydney, Australia.
authors: Emily
authors: E
authors: Blyth
authors: The Westmead Institute for Medical Research, Australia; Blood and Marrow Transplant Unit, Australia; Sydney Cell and Gene Therapy Laboratory, Westmead Hospital, The University of Sydney, Sydney, Australia.
authors: Kenneth P
authors: KP
authors: Micklethwaite
authors: The Westmead Institute for Medical Research, Australia; Blood and Marrow Transplant Unit, Australia; Sydney Cell and Gene Therapy Laboratory, Westmead Hospital, The University of Sydney, Sydney, Australia. Electronic address: david.gottlieb@sydney.edu.au.
authors: David J
authors: DJ
authors: Gottlieb
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018929:Cell Culture Techniques; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes; D015788:HLA-A1 Antigen / Q000097:blood* / Q000276:immunology; D015789:HLA-A2 Antigen / Q000097:blood* / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000939:Epitopes; D015788:HLA-A1 Antigen; D015789:HLA-A2 Antigen; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Herpes simplex virus; adoptive immunotherapy; virus specific T cells