title: Adoptive T-cell therapy of a lung transplanted patient with severe CMV disease and resistance to antiviral therapy.
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.
authors.affiliation: Department of Nephrology and Internal Intensive Care, Universitätsmedizin, Berlin, Germany. gordon.brestrich@charite.de
authors.forename: G
authors.initials: G
authors.lastname: Brestrich
authors.forename: S
authors.initials: S
authors.lastname: Zwinger
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: M
authors.initials: M
authors.lastname: Schmück
authors.forename: A
authors.initials: A
authors.lastname: Röhmhild
authors.forename: M H
authors.initials: MH
authors.lastname: Hammer
authors.forename: A
authors.initials: A
authors.lastname: Kurtz
authors.forename: L
authors.initials: L
authors.lastname: Uharek
authors.forename: C
authors.initials: C
authors.lastname: Knosalla
authors.forename: H
authors.initials: H
authors.lastname: Lehmkuhl
authors.forename: H-D
authors.initials: HD
authors.lastname: Volk
authors.forename: P
authors.initials: P
authors.lastname: Reinke
mesh_terms: D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000209:etiology* / Q000276:immunology / Q000628:therapy* / Q000821:virology; D024882:Drug Resistance, Viral; D018604:Epitope Mapping; D015774:Ganciclovir / Q000494:pharmacology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D016040:Lung Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011024:Pneumonia, Viral / Q000209:etiology* / Q000276:immunology / Q000628:therapy* / Q000821:virology; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D014182:Transplantation, Autologous; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral; D000998:Antiviral Agents; D007371:Interferon-gamma; D015774:Ganciclovir