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Allogeneic gastric cancer cell-dendritic cell hybrids induce tumor antigen (carcinoembryonic antigen) specific CD8+ T cells

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Abstract

The development of protocols for the ex vivo generation of dendritic cells (DCs) has led to intensive research of their potential use in immunotherapy. Accumulating results show the efficacy of this treatment on melanomas which are highly immunogenic. However, its efficacy remains unclear in other tumors. In this study, allogeneic gastric cancer cell–DC hybrids were used to determine the efficacy of this type of immunotherapy in gastric cancer. Fusion cells of DC and allogeneic gastric cancer cells were generated by polyethylene glycol (PEG) and electrofusion. These hybrids were used to induce tumor associated antigen (TAA) specific cytotoxic T lymphocytes (CTLs). The DCs were successfully fused with the allogeneic gastric cancer cells resulting in hybrid cells. These hybrid cells were functional as antigen-presenting cell because they induced allogeneic CD4+ T cells proliferation. CD8+ T cells stimulated by the MKN-45-DC hybrid cells were able to kill MKN-45 when used for immunization. The CTLs killed another gastric cancer cell line, MKN-1, as well as a melanoma cell line, 888mel, suggesting the recognition of a shared tumor antigen. MKN-45 specific CTLs can recognize carcinoembryonic antigen (CEA), indicating that the killing is due to tumor antigens as well as alloantigens. This approach suggests the possible use of allogeneic gastric cancer cell–DC hybrids in DC based immunotherapy for gastric cancer treatment.

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Acknowledgments

We thank Drs. Shinichi Hayashi, Michio Maeta and Nobuaki Kaibara for critically reviewing the manuscript, Dr Yutaka Kawakami for providing the 888mel cell line and Dr Kiyotaka Kuzushima for providing the T2-A24 cell line. We also thank Kirin Brewery Co. for providing the recombinant human GM-CSF, Ono Pharmaceutical Co. for providing the recombinant human IL-4, and Shionogi Pharmaceutical Co. for providing the recombinant human IL-2.

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Authors and Affiliations

  1. Division of Surgical Oncology, Tottori University School of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan

    Sachiko Matsumoto, Hiroaki Saito, Shunichi Tsujitani & Masahide Ikeguchi

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  1. Sachiko Matsumoto
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  2. Hiroaki Saito
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  3. Shunichi Tsujitani
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  4. Masahide Ikeguchi
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Correspondence to Hiroaki Saito.

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Matsumoto, S., Saito, H., Tsujitani, S. et al. Allogeneic gastric cancer cell-dendritic cell hybrids induce tumor antigen (carcinoembryonic antigen) specific CD8+ T cells. Cancer Immunol Immunother 55, 131–139 (2006). https://doi.org/10.1007/s00262-005-0684-3

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  • DOI: https://doi.org/10.1007/s00262-005-0684-3

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