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

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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.

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Acknowledgements

We thank Dr. Roger Lord (University of Tasmania, Australia) for his critical review of the manuscript, Dr. Hiroshi Kikuchi (Blood Transfusion Center of Oita Medical University, Japan) for kindly providing advice on leukapheresis, and Ms. Michiyo Hisaka and Ms. Masae Hikida for their excellent technical support.

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Authors and Affiliations

  1. Department of Surgery I, Oita Medical University, Hasama-machi, 879-5593, Oita, Japan

    Yukio Iwashita, Kouichirou Tahara, Shigeru Goto, Atsushi Sasaki, Seiichiro Kai, Katsunori Kawano & Seigo Kitano

  2. Department of Medicine I, Oita Medical University, Oita, Japan

    Masataka Seike

  3. Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan R.O.C.

    Chao-Long Chen

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  1. Yukio Iwashita
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  2. Kouichirou Tahara
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  3. Shigeru Goto
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  4. Atsushi Sasaki
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  5. Seiichiro Kai
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  6. Masataka Seike
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  7. Chao-Long Chen
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  8. Katsunori Kawano
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  9. Seigo Kitano
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Correspondence to Shigeru Goto.

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Iwashita, Y., Tahara, K., Goto, S. et al. A phase I study of autologous dendritic cell-based immunotherapy for patients with unresectable primary liver cancer. Cancer Immunol Immunother 52, 155–161 (2003). https://doi.org/10.1007/s00262-002-0360-9

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  • DOI: https://doi.org/10.1007/s00262-002-0360-9

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