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Synergism between Human Recombinant -Interferon and Muramyl Dipeptide Encapsulated in Liposomes for Activation of Antitumor Properties in Human Blood Monocytes¹

Department of Cell Biology, The University of Texas at Houston, M. D. Anderson Hospital and Tumor Institute at Houston, Houston, Texas 77030

Highly purified human blood monocytes, isolated by centrifugal elutriation under endotoxin-free conditions, were activated in vitro by combining subthreshold amounts of human recombinant -interferon (r-IFN-) and muramyl dipeptide (MDP) to become tumor cytotoxic against allogeneic A375 melanoma cells. Only intact r-IFN- and MDP produced synergism for human monocyte activation. Neither pH 2-treated r-IFN- and intact MDP nor heat-treated IFN- and intact MDP, nor intact IFN- and the biologically inactive stereoisomer of MDP, N-acetylmuramyl-D-alanyl-D-isoglutamine, produced activation of blood monocytes.

The encapsulation of intact r-IFN- 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- and MDP produced synthetically can be simultaneously delivered to monocytes. Because both r-IFN- 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.

¹ Research was funded in part by Grant 177122 from the Fluor Foundation.

² To whom requests for reprints should be addressed, at Department of Cell Biology, Box 173, The University of Texas, M. D. Anderson Hospital and Tumor Institute, 6723 Bertner Avenue, Houston, TX 77030.

Received 4/ 9/85. Revised 5/23/85. Accepted 6/ 3/85.