PMID- 28090089 OWN - NLM STAT- MEDLINE DCOM- 20171024 LR - 20181113 IS - 1476-5551 (Electronic) IS - 0887-6924 (Linking) VI - 31 IP - 10 DP - 2017 Oct TI - Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT. PG - 2161-2171 LID - 10.1038/leu.2017.16 [doi] AB - 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. FAU - Neuenhahn, M AU - Neuenhahn M AD - Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich, Germany. AD - Clinical Cooperation Group 'Immune Monitoring', Helmholtz Center Munich (Neuherberg) and Technische Universitat Munchen, Munich, Germany. AD - Clinical Cooperation Group ''Antigen-specific Immunotherapy'', Helmholtz Center Munich (Neuherberg) and Technische Universitat Munchen, Munich, Germany. AD - DZIF - National Centre for Infection Research, Munich, Germany. FAU - Albrecht, J AU - Albrecht J AD - Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich, Germany. AD - Clinical Cooperation Group 'Immune Monitoring', Helmholtz Center Munich (Neuherberg) and Technische Universitat Munchen, Munich, Germany. FAU - Odendahl, M AU - Odendahl M AD - Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, Dresden, Germany. FAU - Schlott, F AU - Schlott F AD - Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich, Germany. FAU - Dossinger, G AU - Dossinger G AD - Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich, Germany. FAU - Schiemann, M AU - Schiemann M AD - Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich, Germany. AD - Clinical Cooperation Group ''Antigen-specific Immunotherapy'', Helmholtz Center Munich (Neuherberg) and Technische Universitat Munchen, Munich, Germany. FAU - Lakshmipathi, S AU - Lakshmipathi S AD - Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich, Germany. FAU - Martin, K AU - Martin K AD - Institute of Anaesthesiology, Deutsches Herzzentrum Munchen, Klinik an der Technischen Universitat Munchen, Munich, Germany. FAU - Bunjes, D AU - Bunjes D AD - Department of Internal Medicine III, University of Ulm, Ulm, Germany. FAU - Harsdorf, S AU - Harsdorf S AD - Department of Internal Medicine III, University of Ulm, Ulm, Germany. FAU - Weissinger, E M AU - Weissinger EM AD - Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany. FAU - Menzel, H AU - Menzel H AD - Department of Hematology and Oncology, St Franziskus-Hospital, Flensburg, Germany. FAU - Verbeek, M AU - Verbeek M AD - Department of Internal Medicine III, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany. FAU - Uharek, L AU - Uharek L AD - Medical Clinic Hematology, Oncology and Tumorimmunology, Charite Campus Benjamin Franklin, Berlin, Germany. FAU - Kroger, N AU - Kroger N AD - Bone Marrow Transplantation Unit UKE, Hamburg, Germany. FAU - Wagner, E AU - Wagner E AD - III. Medical Department, Hematology, Oncology and Pneumology, University Medical Center Mainz, Mainz, Germany. FAU - Kobbe, G AU - Kobbe G AD - Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Duesseldorf, Germany. FAU - Schroeder, T AU - Schroeder T AD - Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Duesseldorf, Germany. FAU - Schmitt, M AU - Schmitt M AD - GMP Core Facility, University of Heidelberg, Heidelberg, Germany. FAU - Held, G AU - Held G AD - Internal Medicine I, Jose Carreras Center for Immuno- and Gene Therapy, Saarland University Medical School, Homburg, Saar, Germany. FAU - Herr, W AU - Herr W AD - Department of Internal Medicine III, Haematology and Internal Oncology, University Hospital Regensburg, Regensburg, Germany. FAU - Germeroth, L AU - Germeroth L AD - Juno Cell Therapeutics, formerly Stage Cell Therapeutics, Goettingen, Germany. FAU - Bonig, H AU - Bonig H AD - Institute for Transfusion Medicine and Immunohematology, Johann Wolfgang Goethe University, and German Red Cross Blood Donor Service, Frankfurt, Germany. FAU - Tonn, T AU - Tonn T AD - Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, Dresden, Germany. AD - Transfusion Medicine, Medical Faculty Carl Gustav Carus, Technische Universitat Dresden (TUD), Dresden, Germany. AD - Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany. FAU - Einsele, H AU - Einsele H AD - Department of Internal Medicine II, University Hospital Wurzburg, Wuerzburg, Germany. FAU - Busch, D H AU - Busch DH AD - Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich, Germany. AD - Clinical Cooperation Group 'Immune Monitoring', Helmholtz Center Munich (Neuherberg) and Technische Universitat Munchen, Munich, Germany. AD - Clinical Cooperation Group ''Antigen-specific Immunotherapy'', Helmholtz Center Munich (Neuherberg) and Technische Universitat Munchen, Munich, Germany. AD - DZIF - National Centre for Infection Research, Munich, Germany. AD - Focus Group 'Clinical Cell Processing and Purification', Institute for Advanced Study, Technische Universitat Munchen, Munich, Germany. FAU - Grigoleit, G U AU - Grigoleit GU AD - Department of Internal Medicine II, University Hospital Wurzburg, Wuerzburg, Germany. LA - eng SI - EudraCT/2006-006146-34 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20170116 PL - England TA - Leukemia JT - Leukemia JID - 8704895 RN - 0 (Antiviral Agents) SB - IM MH - Allografts MH - Antiviral Agents/therapeutic use MH - Cytomegalovirus/*immunology MH - Cytomegalovirus Infections/drug therapy/etiology/*therapy/transmission MH - Drug Resistance, Viral MH - Female MH - Graft Survival MH - Hematologic Neoplasms/therapy MH - Hematopoietic Stem Cell Transplantation/*adverse effects MH - Histocompatibility MH - Humans MH - Immunocompromised Host MH - Immunotherapy, Adoptive/adverse effects/*methods MH - Lymphocyte Depletion MH - Male MH - Myelodysplastic Syndromes/therapy MH - Prospective Studies MH - T-Cell Antigen Receptor Specificity MH - T-Lymphocytes/*transplantation MH - Tissue Donors MH - Viremia/drug therapy/etiology/*therapy EDAT- 2017/01/17 06:00 MHDA- 2017/10/25 06:00 CRDT- 2017/01/17 06:00 PHST- 2016/09/03 00:00 [received] PHST- 2016/12/20 00:00 [revised] PHST- 2016/12/30 00:00 [accepted] PHST- 2017/01/17 06:00 [pubmed] PHST- 2017/10/25 06:00 [medline] PHST- 2017/01/17 06:00 [entrez] AID - leu201716 [pii] AID - 10.1038/leu.2017.16 [doi] PST - ppublish SO - Leukemia. 2017 Oct;31(10):2161-2171. doi: 10.1038/leu.2017.16. Epub 2017 Jan 16.