Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT
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 o...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2017
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| In: |
Leukemia
Year: 2017, Volume: 31, Issue: 10, Pages: 2161-2171 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/leu.2017.16 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/leu.2017.16 Verlag, Volltext: https://www.nature.com/articles/leu201716 
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| Author Notes: | 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. Held, W. Herr, L. Germeroth, H. Bonig, T. Tonn, H. Einsele, D.H. Busch and G.U. Grigoleit |
| Summary: | 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. |
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| Item Description: | Advance online publication, 17 February 2017 Gesehen am 28.06.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/leu.2017.16 |