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Blood, 1 June 2002, Vol. 99, No. 11, pp. 3916-3922
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Infusion of cytomegalovirus (CMV)-specific T cells for the
treatment of CMV infection not responding to antiviral chemotherapy
Hermann Einsele,
Eddy Roosnek,
Nathalie Rufer,
Christian Sinzger,
Susanne Riegler,
Jürgen Löffler,
Ulrich Grigoleit,
Arnaud Moris,
Hans-Georg Rammensee,
Lothar Kanz,
Annette Kleihauer,
Friederike Frank,
Gerhard Jahn, and
Holger Hebart
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.
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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