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

214 Citations (Scopus)

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 × 10 6 -1.35 × 10 8 cells/m 2 ) 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
Externally publishedYes

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Epstein-Barr Virus Infections
T-cells
Stem Cell Transplantation
Cytotoxic T-Lymphocytes
Stem cells
Viruses
Adenoviridae
Human Herpesvirus 4
T-Lymphocytes
Virus Diseases
HLA Antigens
Grafts
Therapeutics
Antigens
Viral Structures
Pediatrics
Lymphocytes
Graft vs Host Disease
Antiviral Agents
Blood

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

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

In: Blood, Vol. 114, No. 19, 05.11.2009, p. 4283-4292.

Research output: Contribution to journalArticle

Leen, AM, Christin, A, Myers, GD, Liu, H, Cruz, CR, Hanley, PJ, Kennedy-Nasser, AA, Leung, KS, Gee, AP, Krance, RA, Brenner, MK, Heslop, HE, Rooney, CM & Bollard, CM 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, vol. 114, no. 19, pp. 4283-4292. https://doi.org/10.1182/blood-2009-07-232454
Leen, Ann M. ; Christin, Anne ; Myers, Gary D. ; Liu, Hao ; Cruz, Conrad R. ; Hanley, Patrick J. ; Kennedy-Nasser, Alana A. ; Leung, Kathryn S. ; Gee, Adrian P. ; Krance, Robert A. ; Brenner, Malcolm K. ; Heslop, Helen E. ; Rooney, Cliona M. ; Bollard, Catherine M. / 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. In: Blood. 2009 ; Vol. 114, No. 19. pp. 4283-4292.
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AU - Christin, Anne

AU - Myers, Gary D.

AU - Liu, Hao

AU - Cruz, Conrad R.

AU - Hanley, Patrick J.

AU - Kennedy-Nasser, Alana A.

AU - Leung, Kathryn S.

AU - Gee, Adrian P.

AU - Krance, Robert A.

AU - Brenner, Malcolm K.

AU - Heslop, Helen E.

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