1. Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT.
- Author
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Neuenhahn M, Albrecht J, Odendahl M, Schlott F, Dössinger G, Schiemann M, Lakshmipathi S, Martin K, Bunjes D, Harsdorf S, Weissinger EM, Menzel H, Verbeek M, Uharek L, Kröger N, Wagner E, Kobbe G, Schroeder T, Schmitt M, Held G, Herr W, Germeroth L, Bonig H, Tonn T, Einsele H, Busch DH, and Grigoleit GU
- Subjects
- Allografts, Antiviral Agents therapeutic use, Cytomegalovirus Infections drug therapy, Cytomegalovirus Infections etiology, Cytomegalovirus Infections transmission, Drug Resistance, Viral, Female, Graft Survival, Hematologic Neoplasms therapy, Histocompatibility, Humans, Immunocompromised Host, Immunotherapy, Adoptive adverse effects, Lymphocyte Depletion, Male, Myelodysplastic Syndromes therapy, Prospective Studies, T-Cell Antigen Receptor Specificity, Tissue Donors, Viremia drug therapy, Viremia etiology, Cytomegalovirus immunology, Cytomegalovirus Infections therapy, Hematopoietic Stem Cell Transplantation adverse effects, Immunotherapy, Adoptive methods, T-Lymphocytes transplantation, Viremia therapy
- 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.- Published
- 2017
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