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

Yukio Iwashita, Kouichirou Tahara, Shigeru Goto*, Atsushi Sasaki, Seiichiro Kai, Masataka Seike, Chao Long Chen, Katsunori Kawano, Seigo Kitano

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

115 Scopus citations

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-α (TNF-α) 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 × 106 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.

Original languageEnglish
Pages (from-to)155-161
Number of pages7
JournalCancer Immunology Immunotherapy
Volume52
Issue number3
DOIs
StatePublished - 01 04 2003
Externally publishedYes

Keywords

  • Cell therapy
  • Cholangiocellular carcinoma
  • Delayed-type hypersensitivity
  • Hepatocellular carcinoma
  • Keyhole limpet hemocyanin

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