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

M. Neuenhahn, J. Albrecht, M. Odendahl, F. Schlott, G. Dössinger, M. Schiemann, S. Lakshmipathi, K. Martin, D. Bunjes, S. Harsdorf, E. M. Weissinger, H. Menzel, M. Verbeek, L. Uharek, N. Kröger, E. Wagner, G. Kobbe, T. Schroeder, M. Schmitt, G. HeldW. Herr, L. Germeroth, H. Bonig, T. Tonn, H. Einsele, D. H. Busch, G. U. Grigoleit

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136 Scopus citations

Abstract

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 drug-refractory 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.

Original languageEnglish
Pages (from-to)2161-2171
Number of pages11
JournalLeukemia
Volume31
Issue number10
DOIs
StatePublished - 1 Oct 2017

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