Adoptive immunotherapy of EBV lymphomas

Research output: Contribution to journalArticle

Abstract

Reactivation of EBV after BMT from a mismatched family member or matched unrelated donor, frequently leads to lymphoprolif nation that is often fatal While unmanipulated donor T cells are effective therapy, such treatment is complicated by graft versus host disease. To determine if reconstitution of specific cytotoxic T lymphocyte (CTL) responses can prevent or treat this complication we have administered donor-derived EBV-specLQc CIL lines to patients at high risk after a T cell depleted transplant from a matched unrelated donor or mismatched family member. The cells were marked with the neo gene before 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 three years. The long term persistence of antigen specific CTL may relate to continued presence of EBV antigen or to the presence of CD4 and CDS cells in the infused line. The demonstration that antigen specific CTL can persist and retain their capacity to expand in response to antigenic stimulus, supports the use of these cells for immunotherapy of infection and cancer. None of the 36 patients who received prophylactic CTLs have developed EBV-LPD, compared with a cumulative risk of 11% in patients who did not receive this treatment. Strong evidence of clinically valuable immune activity comes from six 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. Two 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 one patient who received CTLs for bulky established disease developed initial tumor swelling and respiratory obstruction. We conclude that EBV-specic CTLs are safe and effective prophylaxis for EBV lymphoma and can also eradicate established disease. This approach is now being extended to other viruses that produce post-transplant morbidity and to other EBV-associated malignancies.

Original languageEnglish (US)
Number of pages1
JournalAustralian Journal of Medical Science
Volume18
Issue number4
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Hematology
  • Clinical Biochemistry
  • Medical Laboratory Technology
  • Biochemistry, medical
  • Microbiology (medical)

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