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Related Experiment Videos

Immunotherapy for Epstein-Barr virus-associated cancers

C M Rooney1, M A Roskrow, C A Smith

  • 1Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA. cmrooney@msmail.his.tch.tmc.edu

Journal of the National Cancer Institute. Monographs
|August 26, 1998
PubMed
Summary

Adoptively transferred Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) safely prevent EBV-lymphoproliferative disease (EBV-LPD) in transplant patients. CTL therapy also effectively treats existing EBV-LPD, demonstrating long-term persistence and immune reconstitution.

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Area of Science:

  • Immunology
  • Oncology
  • Transplantation Medicine

Background:

  • Epstein-Barr virus (EBV)-associated lymphoproliferative disease (EBV-LPD) is a severe complication post-transplant and in HIV infection.
  • T-cell-depleted allogeneic bone marrow recipients are particularly vulnerable to EBV-LPD.

Purpose of the Study:

  • To evaluate the safety and efficacy of adoptive transfer of gene-marked virus-specific cytotoxic T lymphocytes (CTLs) for EBV-LPD prophylaxis and treatment.
  • To assess CTL homing, persistence, and impact on viral load and immune response.

Main Methods:

  • Gene-marked virus-specific CTLs were adoptively transferred prophylactically or therapeutically to patients undergoing T-cell-depleted allogeneic bone marrow transplantation.
  • Safety, EBV-LPD incidence, tumor regression, CTL homing to tumor sites, and in vivo persistence were monitored.

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Main Results:

  • No toxicity was observed in 42 patients receiving prophylactic CTLs; none developed EBV-LPD compared to 15% in untreated patients.
  • In three patients treated for aggressive EBV-LPD, gene-marked CTLs homed to tumors, leading to complete regression in two.
  • Infused CTLs persisted for up to 3 years, reconstituted EBV-specific immunity, and reduced viral titers significantly.

Conclusions:

  • Adoptive transfer of EBV-specific CTLs is a safe and effective strategy for preventing and treating EBV-LPD in immunocompromised patients.
  • This approach holds promise for treating EBV-positive Hodgkin's disease and potentially EBV-LPD in HIV patients.