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Publication Detail
Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Clinical Trial, Phase I
  • Authors:
    Peggs KS, Thomson K, Samuel E, Dyer G, Armoogum J, Chakraverty R, Pang K, Mackinnon S, Lowdell MW
  • Publication date:
  • Pagination:
    49, 57
  • Journal:
    Clin Infect Dis
  • Volume:
  • Issue:
  • Status:
  • Country:
    United States
  • PII:
  • Language:
  • Keywords:
    Cytomegalovirus, Cytomegalovirus Infections, Humans, Immunotherapy, Adoptive, Interferon-gamma, Stem Cell Transplantation, T-Lymphocytes, Treatment Outcome
BACKGROUND: Adoptive transfer of virus-specific T cells may accelerate reconstitution of antigen-specific immunity and limit the morbidity and mortality of viral infections following allogeneic hematopoietic stem cell transplantation. The logistics of producing virus-specific T cells has, however, limited the application of cellular therapies, particularly following the introduction of more-recent regulatory stipulations. METHODS: We investigated the ability of cytomegalovirus-specific T cells, directly isolated from donor leucapheresates on the basis of interferon γ secretion, to restore antiviral immunity in a group of 25 patients following related-donor transplantation in a single-arm phase I-II study. Selected cells were administered early following transplantation, either after the detection of cytomegalovirus DNA by polymerase chain reaction-based surveillance or prophylactically between day 40 and day 50. RESULTS: Cell selection was successful in all cases, yielding a product biased towards CD4(+) over CD8(+) T cells. The target cell dose of 1 × 10(4) CD3(+) T cells/kg of recipient weight contained a median of 2840 cytomegalovirus-specific CD4(+) cells/kg and 630 cytomegalovirus-specific CD8(+) cells/kg, with a median purity of 43.9% interferon γ-secreting cells. Expansions of both CD4(+) and CD8(+) cytomegalovirus-specific T cells were observed in vivo within days of adoptive transfer. These cells were predominantly terminally differentiated effector-memory cells and showed the same T cell receptor variable β chain (TCRBV) -restriction as the infused cells. They offered protection from reinfection in the majority of patients. CONCLUSIONS: These data indicate that application of cytomegalovirus-specific T cells generated by direct selection using γ-capture is both feasible and effective in a clinical environment. These simple in vitro methodologies should allow more widespread application of virus-specific T cell immunotherapies.
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