UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
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:
    01/01/2011
  • Pagination:
    49, 57
  • Journal:
    Clin Infect Dis
  • Volume:
    52
  • Issue:
    1
  • Status:
    Published
  • Country:
    United States
  • PII:
    ciq042
  • Language:
    eng
  • Keywords:
    Cytomegalovirus, Cytomegalovirus Infections, Humans, Immunotherapy, Adoptive, Interferon-gamma, Stem Cell Transplantation, T-Lymphocytes, Treatment Outcome
Abstract
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.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Author
Research Department of Haematology
Author
Research Department of Haematology
Author
Research Department of Haematology
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by