Journal
BLOOD
Volume 121, Issue 1, Pages 207-218Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-05-430413
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Funding
- National Marrow Donor Program through Amy Strelzer Manasevit Research Program
- Leukemia & Lymphoma Society
- ASBMT Young Investigator Award
- HHV-6 Foundation
- Dan L. Duncan Chair
- Fayez Sarofim Chair
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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. (Blood. 2013; 121(1): 207-218)
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