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Search for immunobiological parameters predictive of clinical effects of OK-432 in patients with malignant ascites

  • Published:
Biotherapy

Abstract

Although OK-432, a potent BRM, has been known to induce the remarkable improvement of clinical conditions in cancer patients through its strong effects on their immune capabilities, no specific immune parameters have been identified to best predict the clinical outcome after the OK-432 treatment. In an attempt to identify early parameters indicative of the clinical effects, we have administered 0.1 mg of OK-432 intraperitoneally to a total of 12 patients with malignant ascites and examined peritoneal fluid and peripheral blood obtained on 4 days before, 1, 3, and 7 days after the OK-432 injection using various immunobiological assays. Four weeks later, clinical improvements were evaluated by the disappearance of malignant cells from and/or substantial decrease in ascites. Four patients (responders) showed the improvements while 8 patients (nonresponders) showed no clinical evidence for improvement. In a few parameters among the many examined, significantly different patterns of changes were noted between responders and nonresponders. Thus, in nonresponder patients MØ and T cell population returned to an initial low level after early increases (on days 1 and/or 3), while they remained increased day 1 through 7 in responders. In responder patients, the cytotoxicity of peritoneal mononuclear cells against K562 and Daudi cells were augmented on day 7, but not in nonresponder patients. Thein vitro stimulation of the mononuclear cells with OK-432 enhanced the cytotoxic activity and induced the interferon (IFN) production in the responders but not in nonresponders. These parameters will be useful for the early prediction of the expected clinical effects of OK-432.

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Abbreviations

BRM:

biological response modifier

FBS:

fetal bovine serum

IAP:

immunosuppressive acidic protein

IFN:

interferon

MØ:

macrophage

PMN:

polymorphonuclear leukocyte

PS:

performance status

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Authors and Affiliations

  1. Department of BRM, Tokyo Institute for Immunopharmacology, Inc., 3-41-8 Takada, Toshima-ku, 171, Tokyo, Japan

    Motoyuki Kataoka, Seiji Hashimoto, Masaki Nanjo, Motoo Saito, Yutaka Sugawara & Takeshi Yoshida

  2. The First Dept. of Surgery, Juntendo University School of Medicine, 113, Tokyo, Japan

    Toshiki Kamano, Motomichi Urabe, Kazuhiko Nishimura & Noburu Sakakibara

Authors
  1. Motoyuki Kataoka
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  2. Seiji Hashimoto
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  3. Masaki Nanjo
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  4. Motoo Saito
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  5. Yutaka Sugawara
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  6. Takeshi Yoshida
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  7. Toshiki Kamano
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  8. Motomichi Urabe
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  9. Kazuhiko Nishimura
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  10. Noburu Sakakibara
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Kataoka, M., Hashimoto, S., Nanjo, M. et al. Search for immunobiological parameters predictive of clinical effects of OK-432 in patients with malignant ascites. Biotherapy 3, 193–201 (1991). https://doi.org/10.1007/BF02171682

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  • DOI: https://doi.org/10.1007/BF02171682

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