Detailed analysis of cytomegalovirus (CMV)-specific T cells expanded for adoptive immunotherapy of CMV infection following allogeneic stem cell transplantation for malignant disease.
Cytotherapy
; 10(3): 289-302, 2008.
Article
em En
| MEDLINE
| ID: mdl-18418774
ABSTRACT
BACKGROUND:
Cytomegalovirus (CMV) infection and its treatment causes significant morbidity following allogeneic stem cell transplantation (SCT) for malignancies. We studied the phenotype, function and growth kinetics of CMV pp65 antigen (Ag)-specific T cells expanded in a short-term culture for adoptive therapy.METHODS:
Peripheral blood mononuclear cells (PBMC) from CMV-seropositive donors were cultured in various conditions with CMV pp65((495-503)) peptide to determine the most effective method for generating CMV-specific T cells. CMV-expanded cultures were tested for frequency, phenotype and functionality using peptide-MHC tetramer analysis, cytokine flow cytometry and cytolytic assays. A patient undergoing allogeneic SCT was administered CMV pp65-specific T cells generated from the donor based on these data, and recipient PBMC were analyzed following T-cell infusion.RESULTS:
CMV pp65-specific T cells were consistently generated from CMV-seropositive donors at high frequencies (20-40% of CD8+ T cells), secreted interferon-gamma (IFN-gamma) in response to CMV peptide and had lytic activity against CMV peptide-expressing targets. Cultured CMV-specific T cells were infused into a SCT recipient without toxicity.DISCUSSION:
Stimulating donor PBMC to generate functional, Ag-specific T cells for infusion into SCT recipients was accomplished consistently using readily available technology. We observed no toxicity in one patient receiving T cells and were able to monitor infused cells. These findings support further study of this approach as a prophylaxis against the risk of infection in patients receiving allogeneic transplantation from CMV-seropositive donors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Imunoterapia Adotiva
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Infecções por Citomegalovirus
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Citomegalovirus
/
Transplante de Células-Tronco
/
Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article