title: 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.
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 x 10(6)-1.35 x 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-mismatched stem cell transplantation and may provide antiviral activity. This trial was registered at www.clinicaltrials.gov as #NCT00590083.
authors.affiliation: Center for Cell and Gene Therapy and Departments of Pediatrics, Immunology, Medicine, and Virology, Baylor College of Medicine, Texas Children's Hospital and the Methodist Hospital, Houston, TX 77030, USA. amleen@txccc.org
authors.forename: Ann M
authors.initials: AM
authors.lastname: Leen
authors.forename: Anne
authors.initials: A
authors.lastname: Christin
authors.forename: Gary D
authors.initials: GD
authors.lastname: Myers
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Conrad R
authors.initials: CR
authors.lastname: Cruz
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hanley
authors.forename: Alana A
authors.initials: AA
authors.lastname: Kennedy-Nasser
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Leung
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Gee
authors.forename: Robert A
authors.initials: RA
authors.lastname: Krance
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Brenner
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
authors.forename: Cliona M
authors.initials: CM
authors.lastname: Rooney
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
mesh_terms: D000258:Adenovirus Infections, Human / Q000209:etiology / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D000260:Adenoviruses, Human / Q000235:genetics / Q000302:isolation & purification; D000293:Adolescent; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D020031:Epstein-Barr Virus Infections / Q000209:etiology / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006650:Histocompatibility Testing; D006801:Humans; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D007223:Infant; D008212:Lymphocyte Depletion; D008297:Male; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation*; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D004279:DNA, Viral
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