Do tuftsin and bestatin constitute a biopharmacological immunoregulatory system?
Tuftsin is the tetrapeptide Thr-Lys-Pro-Arg. It is spontaneously released from the Fc fragment of IgG by two specific enzymes. One 25-micrograms dose administered to mice in good immunologic status stimulated phagocytosis, macrophage killing of tumor cells, delayed hypersensitivity, cytolytic T-cell activity, antibody production, antibody-dependent cell-mediated cytotoxicity (ADCC), and natural killer (NK) cell activity. Administered for 6 months at the dose of 10 micrograms once a week to old, immunodepressed mice, tuftsin restored macrophage and T-cell cytotoxic activities. At this dosage, tuftsin prevented spontaneous tumor development. Tuftsin was also well tolerated in phase I studies in humans in increased polymorphonuclear leukocytes and OKT4-positive lymphocytes. Bestatin is extracted from Streptomyces olivoreticuli. One 100-micrograms dose of bestatin injected in young mice with normal immunologic status increased macrophage cytotoxicity, antibody production, ADCC, and NK cell activities. Long-term administration of bestatin (100 micrograms once a week) corrected macrophage and T-cell cytotoxicity and prevented age-related spontaneous tumors. Bestatin inhibited lymphocyte membrane aminopeptidase, which degrades tuftsin into a tripeptide that is an antagonist competing with it for receptors. Tuftsin and bestatin constitute a biopharmacologic system that can be developed as other aminopeptidase inhibitors are available for study.
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Institut de Cancérologie et d'Immunogénétique (Univ. Paris--Sud, CNRS UA 04-1163; Assoc. Claude-Bernard and ARC), Hôpital Paul-Brousse, Villejuif, France.
D000276:Adjuvants, Immunologic; D000818:Animals; D006801:Humans; D007167:Immunotherapy; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009369:Neoplasms / Q000628:therapy*; D010587:Phagocytosis / Q000187:drug effects; D014405:Tuftsin / Q000494:pharmacology* / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D007930:Leucine; C012211:ubenimex; D014405:Tuftsin