| 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. | |
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MedLine Citation:
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PMID: 19700662 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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 |
Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-08-21 |
Journal Detail:
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Title: Blood Volume: 114 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-11-06 Completed Date: 2009-12-03 Revised Date: 2013-05-15 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 4283-92 Citation Subset: AIM; IM |
Affiliation:
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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 |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00590083 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenovirus Infections, Human
/
etiology,
immunology,
prevention & control*,
therapy* Adenoviruses, Human / genetics, isolation & purification Adolescent Cell Line Child Child, Preschool DNA, Viral / genetics, isolation & purification Epstein-Barr Virus Infections / etiology, immunology, prevention & control*, therapy* Female Herpesvirus 4, Human / genetics, isolation & purification Histocompatibility Testing Humans Immunologic Memory Immunotherapy, Adoptive Infant Lymphocyte Depletion Male Stem Cell Transplantation / adverse effects, methods* T-Lymphocytes, Cytotoxic / immunology*, transplantation* Tissue Donors Transplantation, Homologous |
| Grant Support | |
ID/Acronym/Agency:
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P50 CA126752/CA/NCI NIH HHS; P50 CA126752-04/CA/NCI NIH HHS; RR00188/RR/NCRR NIH HHS; U42 RR16578/RR/NCRR NIH HHS; U54 HL081007/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Viral |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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