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Neuenhahn, M. ; Albrecht, J. ; Odendahl, M.* ; Schlott, F.* ; Doessinger, G.* ; Schiemann, M. ; Lakshmipathi, S.* ; Martin, K.* ; Bunjes, D.* ; Harsdorf, S.* ; Weissinger, E.M.* ; Menzel, H.* ; Verbeek, M.* ; Uharek, L.* ; Kroeger, N.* ; Wagner, E.* ; Kobbe, G.* ; Schroeder, T.* ; Schmitt, M.* ; Held, G.* ; Herr, W.* ; Germeroth, L.* ; Bönig, H.* ; Tonn, T.* ; Einsele, H.* ; Busch, D.H. ; Grigoleit, G.U.*

Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT.

Leukemia 31, 2161-2171 (2017)
Publ. Version/Full Text Research data DOI PMC
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Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed prospectively the safety and efficacy of stem cell-donor-or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a phase I/IIa trial. Allo-HSCT patients with drugrefractory CMV infection and lacking virus-specific T cells were treated with a single dose of ex vivo major histocompatibility complex-Streptamer-isolated CMV epitope-specific donor T cells. Forty-four allo-HSCT patients receiving a T-cell-replete (D+ repl; n = 28) or T-cell-depleted (D+ depl; n = 16) graft from a CMV-seropositive donor were screened for CMV-specific T-cell immunity. Eight D+ depl recipients received adoptive T-cell therapy from their stem cell donor. CMV epitope-specific T cells were well supported and became detectable in all treated patients. Complete and partial virological response rates were 62.5% and 25%, respectively. Owing to longsome third-party donor (TPD) identification, only 8 of the 57 CMV patients transplanted from CMV-seronegative donors (D-) received antigen-specific T cells from partially human leukocyte antigen (HLA)-matched TPDs. In all but one, TPD-derived CMV-specific T cells remained undetectable. In summary, adoptive transfer correlated with functional virus-specific T-cell reconstitution in D+ depl patients. Suboptimal HLA match may counteract expansion of TPD-derived virus-specific T cells in D-patients.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Adoptive Transfer; Cytomegalovirus Disease; Transplantation; Reconstitution; Immunity; Recipients; Therapy; Immunotherapy; Multicenter; Lymphocytes
Language english
Publication Year 2017
HGF-reported in Year 2017
ISSN (print) / ISBN 0887-6924
e-ISSN 1476-5551
Journal Leukemia
Quellenangaben Volume: 31, Issue: 10, Pages: 2161-2171 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
Institute of Molecular Immunology (IMI)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-502700-002
G-501790-003
G-502700-003
G-502700-001
DOI 10.1038/leu.2017.16
WOS ID WOS:000412179600017
Scopus ID 85013031108
PubMed ID 28090089
Erfassungsdatum 2017-10-24
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