Treatment of solid organ transplant recipients with autologous Epstein Barr virus–specific cytotoxic T lymphocytes (CTLs)
| Autor: | John A. Goss, Barbara Savoldo, Petra Reinke, Malcolm K. Brenner, Helen E. Heslop, Milton J. Finegold, Stephen Gottschalk, Teresita Lopez, Stephan Schubert, Adrian P. Gee, Cliona M. Rooney, Ruben E. Quiros-Tejeira, Markus M. Hammer, Lan Zhang, Yu Feng Lin |
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| Rok vydání: | 2006 |
| Předmět: |
Graft Rejection
Male Herpesvirus 4 Human Adoptive cell transfer Clinical Trials and Observations medicine.medical_treatment Immunology medicine.disease_cause Transplantation Autologous Biochemistry Antigen Transplantation Immunology hemic and lymphatic diseases medicine Humans Cytotoxic T cell Antigens Viral Retrospective Studies business.industry ELISPOT Infant Immunosuppression Cell Biology Hematology Immunotherapy Virology Epstein–Barr virus Child Preschool Lymphocyte Transfusion Female business CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Blood. 108:2942-2949 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2006-05-021782 |
| Popis: | We have investigated the in vivo safety, efficacy, and persistence of autologous Epstein Barr virus (EBV)–specific cytotoxic T lymphocytes (CTLs) for the treatment of solid organ transplant (SOT) recipients at high risk for EBV-associated posttransplantation lymphoproliferative disease (PTLD). EBV-CTLs generated from 35 patients expanded with normal kinetics contained both CD8 and CD4 lymphocytes and produced significant specific killing of autologous EBV-transformed B lymphoblastoid cell lines (LCLs). Twelve SOT recipients at high risk for PTLD, or with active disease, received autologous CTL infusions without toxicity. Real-time polymerase chain reaction (PCR) monitoring of EBV-DNA showed a transient increase in plasma EBV-DNA suggestive of lysis of EBV-infected cells, although there was no consistent decrease in virus load in peripheral-blood mononuclear cells. Interferon-γ enzyme-linked immunospot (ELISPOT) assay and tetramer analysis showed an increase in the frequency of EBV-responsive T cells, which returned to preinfusion levels after 2 to 6 months. None of the treated patients developed PTLD. One patient with liver PTLD showed a complete response, and one with ocular disease has had a partial response stable for over one year. These data are consistent with an expansion and persistence of adoptively transferred EBV-CTLs that is limited in the presence of continued immunosuppression but that nonetheless produces clinically useful antiviral activity. |
| Databáze: | OpenAIRE |
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