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Immunomodulatory and therapeutic properties of FK-565 in mice

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Summary

The heptanoyl tripeptide, FK-565 is a biological response modifier with potent therapeutic properties for the treatment of experimental and spontaneous metastases. Doses of FK-565 greater than 5 mg/kg are required for in vivo augmentation of natural killer cells, macrophages, and for therapeutic activity, presumably because FK-565 is a peptide small molecular mass which is rapidly degraded and excreted. Optimal therapeutic activity is observed at approximately 25–50 mg/kg FK-565, administered i.v. three times per week for 4 weeks. In addition to its therapeutic properties, which were consistently greater than the positive control at optimal doses, FK-565 had significant immunoaugmentary properties for natural killer cells, macrophages, and T cells both in vitro and in vivo, suggesting that its therapeutic activity is due to immune augmentation.

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Authors and Affiliations

  1. Department of Immunology, L-101, Smith Kline & French Laboratories, P. O. Box 1539, 19406-0939, King of Prussia, PA, USA

    James E. Talmadge, Barbara Lenz & Mark Schneider

  2. Preclinical Screening Laboratory, Program Resources Inc., Frederick Cancer Research Facility, P.O. Box B, 21701, Frederick, MD, USA

    Hamblin Phillips

  3. National Cancer Institute — Frederick Cancer Research Facility, P. O. Box B, 21701, Frederick, MD, USA

    Cedric Long

Authors
  1. James E. Talmadge
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  2. Barbara Lenz
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  3. Mark Schneider
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  4. Hamblin Phillips
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  5. Cedric Long
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Additional information

This research was sponsored by the DHHS, under contract no. N01-23910 with Program Resources Inc. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government

Abbreviations used: BRM, biological response modifier; MDP, muramyl dipeptide; poly(I,C)-LC poly(I,C)-Lys n polyinosinicpolycytidylic acid complexed with poly(l-lysine) and carboxymethylcellulose; MLR, mixed lymphocyte reaction; MLTR-CMC, mixed lymphocyte tumor response-cell-mediated cytotoxicity; HBSS, Hanks' blanced salts solution; NK, natural killer; IFN, interferon; t. i. w., three times a week

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Talmadge, J.E., Lenz, B., Schneider, M. et al. Immunomodulatory and therapeutic properties of FK-565 in mice. Cancer Immunol Immunother 28, 93–100 (1989). https://doi.org/10.1007/BF00199108

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  • DOI: https://doi.org/10.1007/BF00199108

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