Synergism between Human Recombinant γ -lnterferon and Muramyl Dipeptide Encapsulated in Liposomes for Activation of Antitumor Properties in Human Blood Monocytes

Highly purified human Wood monocytes, isolated by centrifugal elutriation under endotoxin-free conditions, were activated in vitro by combining subthreshold amounts of human recombinant γ -interferon (r-IFN-γ) and muramyl dipeptide (MDP) to become tumor cytotoxic against allogeneic A375 melanoma cells. Only intact r-IFN-γ and MDP produced synergism for human monocyte activation. Neither pH 2-treated r-IFN-γ and intact MDP nor heat-treated IFN-7 and intact MDP, nor intact IFN-γ and the biologically inactive stereoisomer of MDP, N-acetylmuramyl-D-alanyl-_D-isoglutamine, produced activation of blood monocytes. The encapsulation of intact r-IFN-7 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-7 and MDP produced synthetically can be simultaneously delivered to monocytes. Because both r-IFN-7 and MDP can now be produced in large standardized quantities their synergism for activation of tumoricidal properties in human monocytes could be of clinical significance.