Immunotherapeutic strategies to prevent and treat human herpesvirus 6 reactivation after allogeneic stem cell transplantation

Ulrike Gerdemann, Laura Keukens, Jacqueline M. Keirnan, Usha L. Katari, Chinh T.Q. Nguyen, Anne P. De Pagter, Carlos A. Ramos, Alana Kennedy-Nasser, Stephen M. Gottschalk, Helen E. Heslop, Malcolm K. Brenner, Cliona M. Rooney, Ann M. Leen

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Human herpesvirus (HHV) 6 causes substantial morbidity and mortality in the immunocompromised host and has no approved therapy. Adoptive transfer of virus specific T cells has proven safe and apparently effective as prophylaxis and treatment of other virus infections in immunocompromised patients; however, extension to subjects with HHV6 has been hindered by the paucity of information on targets of cellular immunity. We now characterize the cellular immune response from 20 donors against 5 major HHV6B antigens predicted to be immunogenic and define a hierarchy of immunodominance of antigens based on the frequency of responding donors and the magnitude of the T-cell response. We identified specific epitopes within these antigens and expanded the HHV6 reactive T cells using a GMP-compliant protocol. The expanded population comprised both CD4+ and CD8+ T cells that were able to produce multiple effector cytokines and kill both peptide-loaded and HHV6B wild-type virus-infected target cells. Thus, we conclude that adoptive T-cell immunotherapy for HHV6 is a practical objective and that the peptide and epitope tools we describe will allow such cells to be prepared, administered, and monitored in human subjects.

Original languageEnglish (US)
Pages (from-to)207-218
Number of pages12
JournalBlood
Volume121
Issue number1
DOIs
StatePublished - Jan 3 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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