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Herpes simplex virus type 1 (HSV-1) specific T-cell generation from HLA-A1- and HLA-A2-positive donors for adoptive immunotherapy.
- Source :
-
Cytotherapy [Cytotherapy] 2017 Jan; Vol. 19 (1), pp. 107-118. Date of Electronic Publication: 2016 Oct 25. - Publication Year :
- 2017
-
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.<br />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.<br />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.<br />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.<br /> (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1477-2566
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cytotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 27793552
- Full Text :
- https://doi.org/10.1016/j.jcyt.2016.09.013