Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation

Ann M. Leen, Anne Christin, Gary D. Myers, Hao Liu, Conrad R. Cruz, Patrick J. Hanley, Alana A. Kennedy-Nasser, Kathryn S. Leung, Adrian P. Gee, Robert A. Krance, Malcolm K. Brenner, Helen E. Heslop, Cliona M. Rooney, Catherine M. Bollard

Research output: Contribution to journalArticle

228 Scopus citations

Abstract

Viral infection or reactivation remains a major cause of morbidity and mortality after allogeneic stem cell transplantation. We now show that infusions of single cytotoxic T lymphocyte (CTL) lines (5 × 106-1.35 × 108 cells/m2) with specificity for 2 commonly detected viruses, Epstein-Barr virus (EBV) and adenovirus, can be safely administered to pediatric transplantation recipients receiving partially human leukocyte antigen-matched and haploidentical stem cell grafts (n = 13), without inducing graft-versus-host disease. The EBV-specific component of the CTLs expanded in vivo and persisted for more than 12 weeks, but the adenovirus-specific component only expanded in vivo in the presence of concomitant adenoviral infection. Nevertheless, adenovirus-specific T cells could be detected for at least 8 weeks in peripheral blood, even in CTL recipients without viral infection, provided the adenovirus-specific component of their circulating lymphocytes was first expanded by exposure to adenoviral antigens ex vivo. After infusion, none of these 13 high-risk recipients developed EBV-associated lymphoproliferative disease, while 2 of the subjects had resolution of their adenoviral disease. Hence, bispecific CTLs containing both EBV- and adenovirus-specific T cells can safely reconstitute an antigen responsive "memory" population of CTLs after human leukocyte antigen-mis-matched stem cell transplantation and may provide antiviral activity. This trial was registered at www.clinicaltrials.gov as #NCT00590083.

Original languageEnglish (US)
Pages (from-to)4283-4292
Number of pages10
JournalBlood
Volume114
Issue number19
DOIs
StatePublished - Nov 5 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Leen, A. M., Christin, A., Myers, G. D., Liu, H., Cruz, C. R., Hanley, P. J., Kennedy-Nasser, A. A., Leung, K. S., Gee, A. P., Krance, R. A., Brenner, M. K., Heslop, H. E., Rooney, C. M., & Bollard, C. M. (2009). Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation. Blood, 114(19), 4283-4292. https://doi.org/10.1182/blood-2009-07-232454