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Adoptive cellular immunotherapy for EBV lymphoproliferative disease

H E Heslop1, C M Rooney

  • 1Division of Bone Marrow Transplantation, St Jude Children's Research Hospital, Memphis, Tennessee 38103, USA. helen.heslop@stjude.org

Immunological Reviews
|June 1, 1997
PubMed
Summary

Donor-derived Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL) offer safe and effective prophylaxis against EBV-associated lymphoproliferative disease (EBV-LPD) post-bone marrow transplant, and can also treat existing EBV-LPD.

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Area of Science:

  • Immunology
  • Virology
  • Oncology

Background:

  • Reactivation of Epstein-Barr virus (EBV) post-bone marrow transplantation poses a risk for EBV-associated lymphoproliferative disease (EBV-LPD).
  • High-risk patients often receive T-cell-depleted allografts, increasing susceptibility to EBV-LPD.

Purpose of the Study:

  • To evaluate the safety and efficacy of prophylactic and therapeutic administration of donor-derived EBV-specific cytotoxic T lymphocytes (CTL) in patients undergoing bone marrow transplantation.
  • To assess the persistence and immune activity of gene-marked CTLs post-infusion.

Main Methods:

  • Administration of donor-derived, neo gene-marked EBV-specific CTLs to high-risk patients.
  • Monitoring of EBV DNA levels and development of EBV-LPD.
  • In situ hybridization and PCR to track gene-marked CTLs at disease sites.

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Main Results:

  • Prophylactic CTL infusion prevented EBV-LPD in all 36 treated patients, compared to a 14% risk in untreated patients.
  • Elevated EBV DNA levels predictive of lymphoma returned to baseline post-CTL infusion in 6 patients.
  • Two patients with established EBV-LPD achieved prolonged remission after CTL therapy, with selective CTL accumulation at disease sites.

Conclusions:

  • EBV-specific CTLs are a safe and effective prophylactic measure against EBV-LPD after bone marrow transplantation.
  • CTL therapy can also eradicate established EBV-LPD, demonstrating clinically valuable immune activity.
  • This approach holds promise for preventing and treating other post-transplant viral morbidities and EBV-associated malignancies.