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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This work was supported by the Federal Ministry of Education and Research and the SFB (Sonderforschungsbereich/Collaborative Research Centre) TR36 (TP-A10).
LG is an employee of and holds shares in Stage Cell Therapeutics, Göttingen, Germany; now Juno Therapeutics GmbH, Munich, Germany. DHB invented the Streptamer technology and holds shares of Juno Cell Therapeutics Inc. The other authors declare no conflict of interest.
MN, JA, MO, GD, FS, SL, HB, TT, KM and MS performed purification or monitoring analyses; JA, MN and GUG analyzed the data; UG, DHB, HE and LG conceived the study; MN, MO, JA and DHB planned the monitoring experiments; GUG, DHB, SH, EMW, HM, MV, LU, NK, EW, GK, MS and GH were responsibly involved in patient treatment; DHB, HE, TT, HB and LG performed and supervised the clinical cell selection; MN, JA, HB, HE, GUG and DHB wrote the paper.
Supplementary Information accompanies this paper on the Leukemia website
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Neuenhahn, M., Albrecht, J., Odendahl, M. et al. 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). https://doi.org/10.1038/leu.2017.16
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