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A murine plasmacytoma MOPC 104E resistant to cyclophosphamide is resistant to immunotherapy

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Summary

A murine plasmacytoma MOPC 104E (MOPC) is highly sensitive to chemotherapeutic agents such as cyclophosphamide and mitomycin C as well as to immunotherapy (OK-432-combined adoptive immunotherapy using interleukin-2-cultured killer cells). In the present study, we prepared cyclophosphamide-resistant MOPC cells (MOPC-CPA/R) by serial in vivo passage of tumor cells following cyclophosphamide treatment. The in vivo sensitivity of MOPC-CPA/R to mitomycin C or to immunotherapy (OK-432-combined adoptive immunotherapy) was significantly decreased compared to the parent MOPC. In vitro experiments showed that MOPC-CPA/R were more resistant (five-fold) to lysis by cultured immune spleen cells than MOPC. Inhibition of the lytic activity of cultured immune spleen cells against MOPC was significantly increased (P <0.05) by the addition of unlabeled MOPC compared to unlabeled MOPC-CPA/R. These results suggest that MOPC-CPA/R express weaker antigenicity than MOPC. However, the transfer of immune spleen cells cultured with tumor extract derived from MOPC-CPA/R significantly prolonged the survival of MOPC-CPA/R-inoculated mice. Thus, by repeated cyclophosphamide treatment, tumor cells with low-antigenicity were selected. These tumor cells had lower sensitivity to another chemotherapeutic agent and immunotherapy. Such an immunological response may play an important role in cancer therapy.

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Authors and Affiliations

  1. Laboratory of Oncologic Surgery, First Department of Surgery, School of Medicine, Kyoto University, 54 Kawara-cho Shogoin Sakyo-ku, 606, Kyoto, Japan

    Kohei Satoh, Norimichi Kan, Takashi Okino, Masaki Nakanishi, Keiichi Mise, Yasufumi Teramura, Seiji Yamasaki, Kazuhisa Ohgaki & Takayoshi Tobe

Authors
  1. Kohei Satoh
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  2. Norimichi Kan
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  3. Takashi Okino
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  4. Masaki Nakanishi
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  5. Keiichi Mise
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  6. Yasufumi Teramura
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  7. Seiji Yamasaki
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  8. Kazuhisa Ohgaki
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  9. Takayoshi Tobe
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Satoh, K., Kan, N., Okino, T. et al. A murine plasmacytoma MOPC 104E resistant to cyclophosphamide is resistant to immunotherapy. Cancer Immunol Immunother 32, 273–279 (1991). https://doi.org/10.1007/BF01789044

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  • DOI: https://doi.org/10.1007/BF01789044

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