Treatment of solid organ transplant recipients with autologous Epstein Barr virus–specific cytotoxic T lymphocytes (CTLs)

B Savoldo, JA Goss, MM Hammer, L Zhang, T Lopez… - Blood, 2006 - ashpublications.org
B Savoldo, JA Goss, MM Hammer, L Zhang, T Lopez, AP Gee, YF Lin, RE Quiros-Tejeira…
Blood, 2006ashpublications.org
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 …
Abstract
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.
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