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Am J Transplant ; 9(7): 1679-84, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19459791

ABSTRACT

Infections with cytomegalovirus (CMV) can induce severe complications after transplantation, particularly in patients resistant to virostatic therapy. Adoptive transfer of CMV-specific T-cell lines has demonstrated promising results in patients after hematopoietic stem cell transplantation. However, the generation of specific T-cell lines ex vivo and their function in vivo is complicated in solid organ transplant (SOT) recipients. Here, we present the successful adoptive transfer of autologous CMV-specific T cells to a lung transplant recipient with ganciclovir-resistant CMV-pneumonia requiring mechanical ventilation. Infused T cells rapidly expanded in vivo and efficiently inhibited viral replication as confirmed by extensive longitudinal immunological monitoring. After full recovery, the patient was released from the clinic. After 4 weeks, the infection reappeared and persisted at a low level even after a second T-cell infusion. Our experimental data indicate that this could be the consequence of the late differentiated phenotype of the infused T cells and therefore their insufficient longevity in vivo. In summary, our report signifies the high therapeutic potential of adoptive immunotherapy in the treatment of SOT recipients when all other measures show no effect. Further studies have to elucidate the most potent strategies to generate antigen-specific T cells with high functional capacity and robust long-term persistence.


Subject(s)
Cytomegalovirus Infections/etiology , Cytomegalovirus Infections/therapy , Immunotherapy, Adoptive/methods , Lung Transplantation/adverse effects , Lung Transplantation/immunology , Pneumonia, Viral/etiology , Pneumonia, Viral/therapy , T-Lymphocytes/immunology , T-Lymphocytes/transplantation , Amino Acid Sequence , Antigens, Viral/genetics , Antiviral Agents/pharmacology , Cell Line , Cytomegalovirus/genetics , Cytomegalovirus/immunology , Cytomegalovirus/physiology , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , Drug Resistance, Viral , Epitope Mapping , Ganciclovir/pharmacology , Humans , Interferon-gamma/biosynthesis , Male , Middle Aged , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Recurrence , Transplantation, Autologous , Virus Replication
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