1. Herpes simplex virus type 1 (HSV-1) specific T-cell generation from HLA-A1- and HLA-A2-positive donors for adoptive immunotherapy.
- Author
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Ma CK, Clancy L, Deo S, Blyth E, Micklethwaite KP, and Gottlieb DJ
- Subjects
- CD8-Positive T-Lymphocytes immunology, Cell Culture Techniques, Dendritic Cells immunology, Epitopes, HLA-A1 Antigen immunology, HLA-A2 Antigen immunology, Humans, Interferon-gamma metabolism, Interleukin-2 pharmacology, Leukocytes, Mononuclear immunology, T-Lymphocytes drug effects, Tumor Necrosis Factor-alpha metabolism, HLA-A1 Antigen blood, HLA-A2 Antigen blood, Herpesvirus 1, Human immunology, Immunotherapy, Adoptive methods, T-Lymphocytes immunology
- Abstract
Background Aims: 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., Methods: 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., Results: 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., Conclusions: 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., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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