title: Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT.
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.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.|Clinical Cooperation Group 'Immune Monitoring', Helmholtz Center Munich (Neuherberg) and Technische Universität München, Munich, Germany.|Clinical Cooperation Group ''Antigen-specific Immunotherapy'', Helmholtz Center Munich (Neuherberg) and Technische Universität München, Munich, Germany.|DZIF - National Centre for Infection Research, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Neuenhahn
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.|Clinical Cooperation Group 'Immune Monitoring', Helmholtz Center Munich (Neuherberg) and Technische Universität München, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Albrecht
authors.affiliation: Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Odendahl
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Schlott
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Dössinger
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.|Clinical Cooperation Group ''Antigen-specific Immunotherapy'', Helmholtz Center Munich (Neuherberg) and Technische Universität München, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schiemann
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Lakshmipathi
authors.affiliation: Institute of Anaesthesiology, Deutsches Herzzentrum München, Klinik an der Technischen Universität München, Munich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Martin
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Bunjes
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Harsdorf
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: E M
authors.initials: EM
authors.lastname: Weissinger
authors.affiliation: Department of Hematology and Oncology, St Franziskus-Hospital, Flensburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Menzel
authors.affiliation: Department of Internal Medicine III, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Verbeek
authors.affiliation: Medical Clinic Hematology, Oncology and Tumorimmunology, Charité Campus Benjamin Franklin, Berlin, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Uharek
authors.affiliation: Bone Marrow Transplantation Unit UKE, Hamburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Kröger
authors.affiliation: III. Medical Department, Hematology, Oncology and Pneumology, University Medical Center Mainz, Mainz, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Wagner
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Duesseldorf, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Kobbe
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Duesseldorf, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Schroeder
authors.affiliation: GMP Core Facility, University of Heidelberg, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmitt
authors.affiliation: Internal Medicine I, José Carreras Center for Immuno- and Gene Therapy, Saarland University Medical School, Homburg, Saar, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Held
authors.affiliation: Department of Internal Medicine III, Haematology and Internal Oncology, University Hospital Regensburg, Regensburg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Herr
authors.affiliation: Juno Cell Therapeutics, formerly Stage Cell Therapeutics, Goettingen, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Germeroth
authors.affiliation: Institute for Transfusion Medicine and Immunohematology, Johann Wolfgang Goethe University, and German Red Cross Blood Donor Service, Frankfurt, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bonig
authors.affiliation: Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, Dresden, Germany.|Transfusion Medicine, Medical Faculty Carl Gustav Carus, Technische Universität Dresden (TUD), Dresden, Germany.|Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Tonn
authors.affiliation: Department of Internal Medicine II, University Hospital Würzburg, Wuerzburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.|Clinical Cooperation Group 'Immune Monitoring', Helmholtz Center Munich (Neuherberg) and Technische Universität München, Munich, Germany.|Clinical Cooperation Group ''Antigen-specific Immunotherapy'', Helmholtz Center Munich (Neuherberg) and Technische Universität München, Munich, Germany.|DZIF - National Centre for Infection Research, Munich, Germany.|Focus Group 'Clinical Cell Processing and Purification', Institute for Advanced Study, Technische Universität München, Munich, Germany.
authors.forename: D H
authors.initials: DH
authors.lastname: Busch
authors.affiliation: Department of Internal Medicine II, University Hospital Würzburg, Wuerzburg, Germany.
authors.forename: G U
authors.initials: GU
authors.lastname: Grigoleit
mesh_terms: D064591:Allografts; D000998:Antiviral Agents / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000209:etiology / Q000628:therapy* / Q000635:transmission; D024882:Drug Resistance, Viral; D005260:Female; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006648:Histocompatibility; D006801:Humans; D016867:Immunocompromised Host; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D008212:Lymphocyte Depletion; D008297:Male; D009190:Myelodysplastic Syndromes / Q000628:therapy; D011446:Prospective Studies; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000637:transplantation*; D014019:Tissue Donors; D014766:Viremia / Q000188:drug therapy / Q000209:etiology / Q000628:therapy*
chemical_list: D000998:Antiviral Agents