Dendritic cell-based immunotherapy of cancer with carcinoembryonic antigen-derived, HLA-A24-restricted CTL epitope: Clinical outcomes of 18 patients with metastatic gastrointestinal or lung adenocarcinomas

  • Authors:
    • Yuji Ueda
    • Tsuyoshi Itoh
    • Ikuei Nukaya
    • Ichiro Kawashima
    • Kaori Okugawa
    • Yutaro Yano
    • Yoshiki Yamamoto
    • Kei Naitoh
    • Keiji Shimizu
    • Kenichiro Imura
    • Nobuaki Fuji
    • Hitoshi Fujiwara
    • Toshiya Ochiai
    • Hirosumi Itoi
    • Teruhisa Sonoyama
    • Akeo Hagiwara
    • Kazutoh Takesako
    • Hisakazu Yamagishi
  • View Affiliations

  • Published online on: April 1, 2004     https://doi.org/10.3892/ijo.24.4.909
  • Pages: 909-917
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Abstract

We conducted a clinical study of cancer vaccine therapy with dendritic cells (DCs) and HLA-A24-restricted carcinoembryonic antigen (CEA)-derived peptide to assess the feasibility and efficacy of such therapy. Eighteen patients with CEA-expressing metastatic gastrointestinal or lung adenocarcinomas who were positive for human leukocyte antigen (HLA)-A24 were enrolled. DCs were generated from the patients' autologous monocyte-enriched fractions of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells in the presence of granulocyte/macrophage colony-stimulating factor and interleukin-4. The generated DCs were pulsed with CEA-derived, HLA-A24-restricted 9-mer peptide (CEA652) and injected into the patients intradermally and subcutaneously every 2 weeks. Toxicity and clinical and immunological responses were closely monitored in each patient. No severe toxicity directly attributable to the treatment was observed, and the vaccine was well tolerated. Although no definite tumor shrinkage occurred in any patient, long-term stable disease or marked decreases in the serum CEA level were observed in some patients after therapy. Most of the patients in whom treatment was clinically effective showed a positive skin response to CEA652-pulsed DCs (delayed-type hypersensitivity skin test) and a positive in vitro CTL response to CEA652 peptide after therapy. We conclude that active specific immunotherapy using DCs pulsed with CEA652 is a safe and feasible treatment that is clinically effective in some patients with metastatic gastrointestinal or lung adenocarcinomas. Our results will hopefully encourage further refinement and development of DC-based immunotherapy with HLA-A24-restricted CEA-derived peptide for refractory solid cancers that express CEA.

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April 2004
Volume 24 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Ueda, Y., Itoh, T., Nukaya, I., Kawashima, I., Okugawa, K., Yano, Y. ... Yamagishi, H. (2004). Dendritic cell-based immunotherapy of cancer with carcinoembryonic antigen-derived, HLA-A24-restricted CTL epitope: Clinical outcomes of 18 patients with metastatic gastrointestinal or lung adenocarcinomas. International Journal of Oncology, 24, 909-917. https://doi.org/10.3892/ijo.24.4.909
MLA
Ueda, Y., Itoh, T., Nukaya, I., Kawashima, I., Okugawa, K., Yano, Y., Yamamoto, Y., Naitoh, K., Shimizu, K., Imura, K., Fuji, N., Fujiwara, H., Ochiai, T., Itoi, H., Sonoyama, T., Hagiwara, A., Takesako, K., Yamagishi, H."Dendritic cell-based immunotherapy of cancer with carcinoembryonic antigen-derived, HLA-A24-restricted CTL epitope: Clinical outcomes of 18 patients with metastatic gastrointestinal or lung adenocarcinomas". International Journal of Oncology 24.4 (2004): 909-917.
Chicago
Ueda, Y., Itoh, T., Nukaya, I., Kawashima, I., Okugawa, K., Yano, Y., Yamamoto, Y., Naitoh, K., Shimizu, K., Imura, K., Fuji, N., Fujiwara, H., Ochiai, T., Itoi, H., Sonoyama, T., Hagiwara, A., Takesako, K., Yamagishi, H."Dendritic cell-based immunotherapy of cancer with carcinoembryonic antigen-derived, HLA-A24-restricted CTL epitope: Clinical outcomes of 18 patients with metastatic gastrointestinal or lung adenocarcinomas". International Journal of Oncology 24, no. 4 (2004): 909-917. https://doi.org/10.3892/ijo.24.4.909