Adoptive cellular immunotherapy for EBV lymphoproliferative diseases

Publisher Website
Google Scholar
Abstract
Summary: Reactivation of EBV (Epstein‐Barr virus) after bone marrow transplantation can result in EBV‐associated lymphoproliferative disease (EBV‐LPD), We have administered donor‐derived EBV‐specific cytotoxic T lymphocytes (CTL) to patients who are at high risk of this complication after receiving a T‐cell‐depleted allograft from a matched unrelated or mismatched related donor. The cells were marked with (he neo GENE U fore infusion so that we could evaluate their persistence and efficacy, CTL infusion produced a virus‐specific immune response to EBV that persisted for up to 2 years. None of the 36 patients who received prophylactic CTLs have developed EBV‐LPD compared with a cumulative risk of 14% in patients who did not receive this treatment. Strong evidence of clinically valuable immune activity conies from 6 of these 36 patients whose pre‐CTL levels of EBV DNA were elevated to a degree strongly predictive of the onset of lymphoma. In each of these cases, the levels returned to baseline after CTL infusion. 2 patients who were treated for clinically evident EBV‐LPD attained prolonged remission after CTL infusion and in situ hybridization and semiquantitative PCR showed that the gene‐marked CTL had selectively accumulated at disease sites, The prophylactic CTL treatment lacked acute adverse effects, whereas 1 patient who received CTLs for bulky established disease developed initial tumor swelling and respiratory obstruction. We conclude that EBV‐specific CTLs are a safe and effective prophylaxis for EBV lymphoma and can also eradicate established disease. This approach is now being extended lo other viruses that produce post‐trans‐plant morbidity and to other EBV‐associated malignancies.