Infusion of cytomegalovirus (CMV)–specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy

Einsele, Hermann; Roosnek, Eddy; Rufer, Nathalie; Sinzger, Christian; Riegler, Susanne; Löffler, Jürgen; Grigoleit, Ulrich; Moris, Arnaud; Rammensee, Hans-Georg; Kanz, Lothar; Kleihauer, Annette; Frank, Friederike; Jahn, Gerhard; Hebart, Holger

doi:10.1182/blood.v99.11.3916

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Journal article

Infusion of cytomegalovirus (CMV)–specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy

Einsele, Hermann From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.
Roosnek, Eddy From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.
Rufer, Nathalie From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.
Sinzger, Christian From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.
Riegler, Susanne From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.
Löffler, Jürgen From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.
Grigoleit, Ulrich From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.
Moris, Arnaud From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.
Rammensee, Hans-Georg From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.
Kanz, Lothar From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.
Kleihauer, Annette From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.
Frank, Friederike From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.
Jahn, Gerhard From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.
Hebart, Holger From the Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany; Division of Immunology and Allergology, University of Geneva, Switzerland; National Center for Competence and Research Molecular Oncology, Swiss Institut for Experimental Cancer Research, Epalinges, Switzerland; Abteilung Medizinische Virologie und Epidemiologie der Viruskrankheiten, Tübingen, Germany; and Institut für Zellbiologie Universität Tübingen, Germany.

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Blood. - American Society of Hematology. - 2002, vol. 99, no. 11, p. 3916-3922

English We adoptively transferred donor-derived cytomegalovirus (CMV)-specific T-cell lines into 8 stem cell transplant recipients lacking CMV-specific T-cell proliferation. All patients, of whom one was infected by a CMV strain that was genotypically ganciclovir resistant, had received unsuccessful antiviral chemotherapy for more than 4 weeks. CMV-specific lines had been prepared by repetitive stimulation with CMV antigen, which increased the percentage of CMV-specific T cells and ablated alloreactivity completely even against patients mismatched for 1 to 3 HLA antigens. After transfer of 107 T cells/m2 at a median of 120 days (range, 79-479 days) after transplantation, no side effects were noticed. Despite cessation of antiviral chemotherapy, the CMV load dropped significantly in all 7 evaluable patients, with a maximal reduction after a median of 20 days (range, 5-31 days). In 2 patients with high virus load, the antiviral effect was only transient. One of these patients received a second T-cell infusion, which cleared the virus completely. At a median of 11 days after transfer, CMV-specific T-cell proliferation was demonstrated in 6 patients, and an increase in CMV-specific CD4+ T cells was demonstrated in 5 patients. In 6 patients, 1.12 to 41 CMV-specific CD8+ T cells/μL blood were detected at a median of 13 days after transfer, with an increase in all patients lacking CMV-specific CD8+ T cells prior to transfer. Hence, anti-CMV cellular therapy was successful in 5 of 7 patients, whereas in 2 of 7 patients, who received an intensified immune suppression at the time of or after T-cell therapy, only transient reductions in virus load were obtained.

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English

Open access status

green

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DOI 10.1182/blood.v99.11.3916
ISSN 1528-0020

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https://folia.unifr.ch/global/documents/52963

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Journal article

Infusion of cytomegalovirus (CMV)–specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy

Immunology

Cell Biology

Biochemistry

Hematology

Statistics