Small molecular microbial products enhancing immune response.

Plasmids are involved in the biosynthesis of many microbial secondary metabolites, and compounds which have various chemical structures are produced by microorganisms. Therefore, it is possible to find microbial products which have no antimicrobial activities but pharmacological activities. Aminopeptidases, alkaline phosphatase and esterase have been found to appear on the cell surface and their strong inhibitors have been confirmed to enhance or decrease immune response. These inhibitors have a very low toxicity without cytotoxic action. Bestatin, which inhibited aminopeptidase B and leucine aminopeptidase, enhanced delayed-type hypersensitivity in a wide range of its low dosis (0.1-100 micrometer/mouse) and produced an immune resistance to the second inoculation of the same tumor cells. It showed a synergistic action with antitumor agents in treatment of experimental tumors. Treatment with bestatin alone exhibited a strong therapeutic effect on slowly growing solid tumors.