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Detailed analysis of cytomegalovirus (CMV)-specific T cells expanded for adoptive immunotherapy of CMV infection following allogeneic stem cell transplantation for malignant disease.

Publication ,  Journal Article
Hobeika, A; Osada, T; Serra, D; Peplinski, S; Hanson, K; Tanaka, Y; Niedzwiecki, D; Chao, N; Rizzieri, D; Lyerly, H; Clay, T; Morse, M
Published in: Cytotherapy
2008

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.

Duke Scholars

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Published In

Cytotherapy

DOI

EISSN

1477-2566

Publication Date

2008

Volume

10

Issue

3

Start / End Page

289 / 302

Location

England

Related Subject Headings

  • Transplantation, Homologous
  • T-Lymphocytes
  • Stem Cell Transplantation
  • Receptors, Antigen, T-Cell, alpha-beta
  • Phenotype
  • Peptides
  • Neoplasms
  • Lymphocyte Activation
  • Kinetics
  • Immunotherapy, Adoptive
 

Citation

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Hobeika, A., Osada, T., Serra, D., Peplinski, S., Hanson, K., Tanaka, Y., … Morse, M. (2008). 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. https://doi.org/10.1080/14653240801927040
Hobeika, Ac, T. Osada, D. Serra, S. Peplinski, K. Hanson, Y. Tanaka, D. Niedzwiecki, et al. “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, no. 3 (2008): 289–302. https://doi.org/10.1080/14653240801927040.
Hobeika A, Osada T, Serra D, Peplinski S, Hanson K, Tanaka Y, Niedzwiecki D, Chao N, Rizzieri D, Lyerly H, Clay T, Morse M. Detailed analysis of cytomegalovirus (CMV)-specific T cells expanded for adoptive immunotherapy of CMV infection following allogeneic stem cell transplantation for malignant disease. Cytotherapy. 2008;10(3):289–302.
Journal cover image

Published In

Cytotherapy

DOI

EISSN

1477-2566

Publication Date

2008

Volume

10

Issue

3

Start / End Page

289 / 302

Location

England

Related Subject Headings

  • Transplantation, Homologous
  • T-Lymphocytes
  • Stem Cell Transplantation
  • Receptors, Antigen, T-Cell, alpha-beta
  • Phenotype
  • Peptides
  • Neoplasms
  • Lymphocyte Activation
  • Kinetics
  • Immunotherapy, Adoptive