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

Neuenhahn M, Albrecht J, Odendahl M, Schlott F, Doessinger G, Schiemann M, Lakshmipathi S, Martin K, Bunjes D, Harsdorf S, Weissinger EM, Menzel H, Verbeek M, Uharek L, Kroeger N, Wagner E, Kobbe G, Schroeder T, Schmitt M, Held G, Herr W, Germeroth L, Bonig H, Tonn T, Einsele H, Busch DH, Grigoleit GU (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 31

Pages Range: 2161-2171

Journal Issue: 10

DOI: 10.1038/leu.2017.16

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.

Involved external institutions

Technische Universität München (TUM) Germany (DE) DRK-Blutspendedienst Nord-Ost gemeinnützige GmbH Germany (DE) Klinikum rechts der Isar Germany (DE) Universität Ulm Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) St. Franziskus-Hospital Münster Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) Heinrich-Heine-Universität Düsseldorf Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Universität des Saarlandes (UdS) Germany (DE) Universitätsklinikum Regensburg Germany (DE) Goethe-Universität Frankfurt am Main Germany (DE) Technische Universität Dresden Germany (DE) Universitätsklinikum Würzburg Germany (DE)

How to cite

APA:

Neuenhahn, M., Albrecht, J., Odendahl, M., Schlott, F., Doessinger, G., Schiemann, M.,... Grigoleit, G.U. (2017). Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT. Leukemia, 31(10), 2161-2171. https://doi.org/10.1038/leu.2017.16

MLA:

Neuenhahn, 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 31.10 (2017): 2161-2171.

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