Do tuftsin and bestatin constitute a biopharmacological immunoregulatory system?

Abstract

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.

• Authors: G Mathé
• Journal: Cancer detection and prevention. Supplement : official publication of the International Society for Preventive Oncology, Inc (Cancer Detect Prev Suppl) Vol. 1 Pg. 445-55 ( 1987) ISSN: 1043-6995 [Print] United States
• PMID: 3319151 (Publication Type: Journal Article, Review)

Chemical References

• Adjuvants, Immunologic
• Leucine
• ubenimex
• Tuftsin

Topics

• Adjuvants, Immunologic
• Animals
• Humans
• Immunotherapy
• Leucine (analogs & derivatives, pharmacology, therapeutic use)
• Neoplasms (therapy)
• Phagocytosis (drug effects)
• Tuftsin (pharmacology, therapeutic use)