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Related Experiment Videos

Immunotherapy for Hodgkin's disease.

C M Rooney1, C Bollard, M H Huls

  • 1Centre for Cell and Gene Therapy, Department of Pediatrics, Division of Hematology and Oncology, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.

Annals of Hematology
|March 4, 2003
PubMed
Summary

EBV-specific T-cells show promise in treating Hodgkin's Disease by targeting malignant cells. While effective in reducing viral load and some symptoms, further research is needed to overcome immune evasion strategies for complete remission.

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Area of Science:

  • Immunology
  • Oncology
  • Virology

Background:

  • Epstein-Barr virus (EBV) proteins are targets for immunotherapy in Hodgkin's Disease (HD).
  • HD tumors employ immune evasion tactics, like down-regulating EBV antigens and secreting TGF-beta, to resist T-cell attacks.
  • Cytotoxic T lymphocytes (CTL) must overcome these host defenses to be effective.

Purpose of the Study:

  • To evaluate the efficacy of EBV-specific CTL therapy in patients with relapsed HD.
  • To investigate strategies for enhancing CTL effectiveness against HD immune evasion mechanisms.

Main Methods:

  • EBV-specific CTL were generated ex vivo from patients' peripheral blood mononuclear cells (PBMC) using autologous EBV-transformed lymphoblastoid cells (LCL) for stimulation.
  • Thirteen patients with multiply relapsed HD received CTL infusions.

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  • Pre-clinical studies explored enhancing CTL specificity (LMP1, LMP2) and resistance to TGF-beta via genetic modification (dominant-negative TGF-beta receptor, IL-12).

    • Main Results:

    • CTL infusion led to increased EBV-specific immunity, decreased viral load, and CTL homing to tumors, persisting up to 10 months.
    • Clinical responses included resolution of B symptoms and partial tumor responses, with one complete remission of residual disease post-transplant.
    • No complete remission was achieved in bulky disease; low frequencies of LMP2-specific CTL were observed in infused lines.

    Conclusions:

    • EBV-specific CTL therapy can induce anti-tumor immune responses and clinical benefits in relapsed HD.
    • Strategies to improve CTL antigen specificity and resistance to tumor-secreted immunosuppressive factors like TGF-beta are crucial for future therapeutic development.
    • Further clinical trials are warranted to optimize CTL-based immunotherapy for HD.