A phase I study of autologous dendritic cell-based immunotherapy for patients with unresectable primary liver cancer

Cancer Immunol Immunother. 2003 Mar;52(3):155-61. doi: 10.1007/s00262-002-0360-9. Epub 2003 Feb 6.

Abstract

Background/aims: To evaluate the safety and feasibility of immunotherapy based on autologous dendritic cells (DC) for patients with unresectable primary liver cancer (PLC).

Methods: A total of ten patients were enrolled and immunized with DCs. Autologous DCs were generated ex vivo in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). Cells were then pulsed with tumor lysate (TL), tumor necrosis factor-alpha (TNF-alpha) and keyhole limpet hemocyanin (KLH). Non-adherent cells were collected on day 9 and cells were administered into the inguinal lymph node. Each patient received 1-10 x 10(6) cells four times at weekly intervals.

Results: Immunization was well tolerated in all patients without significant toxicity. DC vaccination induced delayed-type hypersensitivity (DTH) against KLH in seven out of ten patients. In one patient, one of the two liver tumors (tumor in segment 7, 13 mm in diameter) decreased in size to 7 mm and showed necrotic change on computed tomography examination after eight immunizations. In two patients, serum levels of tumor markers decreased after vaccination.

Conclusion: The present clinical trial suggested that immunization by TL-pulsed DCs is feasible in patients with unresectable PLC without any toxicity. Further improvement in the clinical results of immunotherapy might be expected by modifying the therapeutic protocol.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / therapy*
  • Cell Separation
  • Dendrites / immunology*
  • Dendrites / metabolism
  • Dendritic Cells
  • Female
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Hemocyanins / pharmacology
  • Humans
  • Hypersensitivity, Delayed
  • Immunotherapy / methods*
  • Interleukin-4 / pharmacology
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / therapy*
  • Lymph Nodes / metabolism
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Phenotype
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Hemocyanins
  • keyhole-limpet hemocyanin