Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy.
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 10(7) T cells/m(2) 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/microL 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.
Einsele
Hermann
H
Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany. hneisel@med.uni-tuebingen.de
Roosnek
Eddy
E
Rufer
Nathalie
N
Sinzger
Christian
C
Riegler
Susanne
S
Löffler
Jürgen
J
Grigoleit
Ulrich
U
Moris
Arnaud
A
Rammensee
Hans-Georg
HG
Kanz
Lothar
L
Kleihauer
Annette
A
Frank
Friederike
F
Jahn
Gerhard
G
Hebart
Holger
H
D019264:Adoptive Transfer / Q000009:adverse effects; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000628:therapy*; D006086:Graft vs Host Disease / Q000453:epidemiology; D006801:Humans; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D008285:Major Histocompatibility Complex / Q000276:immunology; D008875:Middle Aged; D008991:Monitoring, Physiologic; D013601:T-Lymphocytes / Q000637:transplantation* / Q000821:virology; D017211:Treatment Failure; D019562:Viral Load; D014916:Whole-Body Irradiation
D000998:Antiviral Agents