SYNERGISM BETWEEN HUMAN RECOMBINANT GAMMA-INTERFERON AND MURAMYL DIPEPTIDE ENCAPSULATED IN LIPOSOMES FOR ACTIVATION OF ANTITUMOR PROPERTIES IN HUMAN-BLOOD MONOCYTES

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (12) , 6188-6193
Abstract
Highly purified human blood monocytes, isolated by centrifugal elutriation under endotoxin-free conditions, were activated in vitro by combining subthreshold amounts of human recombinant .gamma.-interferon (r-IFN-.gamma.) and muramyl dipeptide (MDP) to become tumor cytotoxic against allogeneic A375 melanoma cells. Only intact r-IFN-.gamma. and MDP produced synergism for human monocyte activation. Neither pH 2-treated r-IFN-.gamma. and intact MDP nor heat-treated IFN-.gamma. and intact MDP, nor intact IFN-.gamma. and the biologically inactive stereoisomer of MDP, N-acetylmuramyl-D-alanyl-D-isoglutamine, produced activation of blood monocytes. The encapsulation of intact r-IFN-.gamma. and MDP within the same preparation of multilamellar liposomes was synergistic for monocyte activation. These data show that synergism for monocyte activation can be produced by human r-IFN-.gamma. and MDP produced synthetically can be simultaneously delivered to monocytes. Because both r-IFN-.gamma. and MDP can now be produced in large standarized quantities their synergism for activation of tumoricidal properties in human monocytes could be of clinical significance.

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