Summary
We examined the activation to the tumoricidal state of normal mouse peritoneal exudate macrophages, bone marrow macrophages, and human blood monocytes by liposomes containing either lipophilic muramyl tripeptide (CGP 19 835) or a new synthetic analogue of lipoprotein from gram-negative bacteria outer wall, CGP 31 362, or combinations of the two. The superiority of liposomes containing the synthetic lipopeptide over liposomes containing lipophilic muramyl tripeptide for in vitro activation of monocytes and macrophages was demonstrated in several experiments. First, liposome-CGP-19 835 activated monocytes only in the presence of interferon-γ, whereas activation with liposome-CGP 31 362 was interferon-independent. Second, activation of both mouse macrophages and human blood monocytes by liposome-CGP 31 362 occurred at a lower liposomal concentration than that by liposome-CGP 19 835. Third, monocytes incubated with liposome-CGP 31 362 released both tumor necrosis factor (TNF) and interleukin-1 activities, whereas monocytes treated with liposome-CGP 19 835 (in the absence of interferon-γ) released only TNF activity. These data suggest that liposomes containing the synthetic lipopeptide CGP 31 362 are superior to liposomes containing CGP 19 835 for systemic activation of macrophages.
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References
Adams DO, Marino PA (1981) Evidence for a multistep mechanism of cytolysis by BCG-activated macrophages: the interrelationship between the capacity for cytolysis, target binding, and secretion of cytolytic factor. J Immunol 126: 981
Adams DO, Kao K-J, Farb R, Pizzo SV (1980) Effector mechanisms of cytolytically activated macrophages: II. Secretion of a cytolytic factor by activated macrophages and its relationship to secreted neural proteases. J Immunol 124: 293
Alving CR (1983) Delivery of liposome-encapsulated drugs to macrophages. Pharmacol Ther 22: 407
Brodt P, Blore J, Phillips NC, Munzer JS, Rioux JD (1989) Inhibition of murine hepatic tumor growth by liposomes containing a lipophilic muramyl dipeptide. Cancer Immunol Immunother 28: 54
Currie GA, Basham C (1978) Differential arginine dependence and the selective cytotoxic effects of activated macrophages for malignant cells in vitro. Br J Cancer 38: 653
Daous SS, Hume LR, Juliano R (1989) Liposomes in cancer therapy. Adv Drug Delivery Rev 3: 405
Decker T, Lohmann-Mathes ML, Gifford GE (1987) Cell-associated tumor necrosis factor (TNF) as a killing mechanism of activated cytotoxic macrophages. J Immunol 138: 957
Ferluga J, Schorlemmer HU, Baptista LC, Allison AC (1978) Production of the complement cleavage product, C3a, by activated macrophages and its tumorilytic effects. Clin Exp Immunol 31: 512
Fidler IJ (1981) The in situ induction of tumoricidal activity in alveolar macrophages by liposomes containing muramyl dipeptide is a thymus-independent process. J Immunol 127: 1719
Fidler IJ (1985) Macrophages and metastasis: a biological approach to cancer therapy. Cancer Res 45: 4714
Fidler IJ (1986) Immunomodulation of macrophages for cancer and antiviral therapy. In: Tomlinson E, Davis SS (eds) Site-specific drug delivery. Wiley, New York, p 111
Fidler IJ (1988) Targeting of immunomodulators to mononuclear phagocytes for therapy of cancer. Adv Drug Delivery Rev 2: 69
Fidler IJ, Raz A, Fogler WE, Kirsh R, Bugelski P, Poste G (1980) The design of liposomes to improve delivery of macrophage-augmenting agents to alveolar macrophages. Cancer Res 40: 4460
Fidler IJ, Sone S, Fogler WE, Barnes ZL (1981) Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide. Proc Natl Acad Sci USA 78: 1680
Fidler IJ, Sone S, Fogler WE, Smith D, Braun DG, Tarcsay L, Gisler RJ, Schroit AJ (1982) Efficacy of liposomes containing a lipophilic muramyl dipeptide for activating the tumoricidal properties of alveolar macrophages in vivo. J Biol Response Modif 1: 43
Fidler IJ, Fogler WE, Tarcsay L, Schumann G, Braun DG, Schroit AJ (1983) Systemic activation of macrophages and treatment of cancer metastases by liposomes containing hydrophilic or lipophilic muramyl dipeptide. Immunopharmacology 2: 253
Fidler IJ, Fogler WE, Kleinerman ES, Saiki I (1985) Abrogation of species specificity for activation of tumoricidal properties in macrophages by recombinant mouse or human gamma interferon encapsulated in liposomes. J Immunol 135: 4289
Fidler IJ, Jessup JM, Fogler WE, Staerkel R, Mazumder A (1986) Activation of tumoricidal properties in peripheral blood monocytes of patients with colorectal carcinoma. Cancer Res 44: 994
Fidler IJ, Fan D, Ichinose Y (1989) Potent in situ activation of murine lung macrophages and therapy of melanoma metastases by systemic administration of liposomes containing muramyltripeptide phosphatidylethanolamine and interferon gamma. Invasion Metastasis 9: 75
Fidler IJ, Nii A, Utsugi T, Brown D, Bakouche O, Kleinerman ES (1990) Differential release of TNF-α, IL-1, and PGE2 by human blood monocytes subsequent to interaction with different bacterial derived agents. Lymphokine Res 9: 449
Fogler WE, Fidler IJ (1984) Modulation of the immune response by muramyl dipeptide. In: Chirigos MA, Fenichel RL (eds) Immune modulation agents and their mechanisms. Dekker, New York, p 499
Fogler WE, Fidler IJ (1986) The activation of tumoricidal properties in human blood monocytes by muramyl dipeptide requires specific intracellular interaction. J Immunol 136: 2311
Fogler WE, Wade R, Brundish DE, Fidler IJ (1985) Distribution and fate of free and liposome-encapsulated [3H]nor-muramyl dipeptide and [3H]muramyl tripeptide phosphatidylethanolamine in mice. J Immunol 135: 1372
Gisler RH, Dietrich FM, Baschang G, Brownbill A, Schumann G, Staber FB, Tarcsay L (1979) New developments in drugs enhancing the immune response: activation of lymphocytes and accessory cells by muramyl peptides. In: Turk JL, Danker D (eds) Immune responsiveness. MacMillan, London, p 133
Heicappell R, Naito S, Ichinose Y, Creasy AA, Lin LS, Fidler IJ (1987) Cytostatic and cytolytic effects of human recombinant tumor necrosis factor on human renal cell carcinoma cell lines derived from a single surgical specimen. J Immunol 138: 1634
Hibbs JB, Taintor RR, Vavrin Z (1987) Macrophage cytotoxicity: role forl-arginine deiminase and imino nitrogen oxidation to nitrite. Science 235: 473
Hudson MM, Snyder JS, Jaffe N, Kleinerman ES (1988) In vitro and in vivo effect of Adriamycin therapy on monocyte activation by liposome-encapsulated immunomodulators. Cancer Res 48: 5256
Hume DA, Gordon S (1983) Optimal conditions for proliferation of bone marrow-derived mouse macrophages in culture: the roles of CSF-1, serum, Ca2+, and adherence. J Cell Physiol 117: 189
Hume DA, Allan W, Golder J, Stephens RW, Dow WF, Warren HS (1985) Preparation and characterization of human bone marrow-derived macrophages. J Leukocyte Biol 38: 541
Ichinose Y, Bakouche O, Tsao JY, Fidler IJ (1988) Tumor necrosis factor and IL-1 associated with plasma membranes of activated human monocytes lyse monokine-sensitive but not monokine-resistant tumor cells whereas viable activated monocytes lyse both. J Immunol 141: 512
Ichinose Y, Tsao JY, Fidler IJ (1988) Destruction of tumor cells by monokines released from activated human blood monocytes: evidence for parallel and additive effects of IL-1 and TNF. Cancer Immunol Immunother 27: 7
Kaplow LS (1965) Simplified myeloperosidase stain using benzidine dihydrochloride. Blood 26: 215
Keller R, Geiges M, Keist R (1990)l-Arginine-dependent reactive nitrogen intermediates as mediators of tumor cell killing by activated macrophages. Cancer Res 50: 1421
Kleinerman ES, Hudson MM (1989) Liposome therapy: a novel approach to the treatment of childhood osteosarcoma. In: Lopez-Berestein G, Fidler IJ (eds) Liposomes in the therapy of infectious diseases and cancer, new series, vol 89. Liss, New York, p 71
Kleinerman ES, Fogler WE, Fidler IJ (1985) Intracellular activation of human and rodent macrophages by human lymphokines encapsulated in liposomes. J Leukocyte Biol 37: 571
Koff WC, Fidler IJ (1985) The potential use of liposome-mediated antiviral therapy. Antiviral Res 228: 495
Lachman LB, Dinarello CA, Llansa ND, Fidler IJ (1986) Natural and recombinant human interleukin 1-β is cytotoxic for human melanoma cells. J Immunol 136: 3098
MacEwen EG, Kurzman ID, Rosenthal RC, Smith BW, Manley PA, Roush JK, Howard PE (1989) Therapy for osteosarcoma in dogs with intravenous injection of liposome-encapsulated muramyl tripeptide. J Natl Cancer Inst 81: 935
Matsushima K, Taguchi M, Kovacs EJ, Young HA, Oppenheim JJ (1986) Intracellular localization of human monocyte associated interleukin 1 (IL-1) from monocytes by trypsin and plasmin. J Immunol 136: 2883
Mehta K, Lopez-Berestein G, Hersh EM, Juliano RL (1982) Uptake of liposomes and liposome-encapsulated muramyl dipeptide by human peripheral blood monocytes. J Reticuloendothelial Soc 1982: 155
Mourad N (1968) A simple method for obtaining platelet concentrations free of aggregates. Transfusion 8: 48
Murray JL, Kleinerman ES, Cunningham JE, Tatom JR, Andrejcio K, Lepe-Zuniga J, Lamki LM, Rosenblum MG, Frost H, Gutterman JU, Fidler IJ (1989) Phase I trial of liposomal muramyl-tripeptide-phosphatidylethanolamine [MTP-PE (CGP 19 835 A)] in cancer patients. J Clin Oncol 7: 915
Nathan CF (1987) Secretory products of macrophages. J Clin Invest 79: 319–327
Nathan CF, Silverstein SC, Brukner LH, Cohn ZA (1979) Extracellular cytolysis by activated macrophages and granulocytes: II. Hydrogen peroxide as a mediator of cytotoxicity. J Exp Med 149: 100
Onozaki K, Matsushima K, Aggarwal BB, Saito T, Oppenheim JJ (1985) Human interleukin 1 is a cytocidal factor for several tumor cell lines. J Immunol 135: 3862
Phillips NC, Tsao M (1989) Inhibition of experimental liver tumor growth in mice by liposomes containing a lipophilic muramyl dipeptide. Cancer Res 49: 936
Phillips NC, Mora ML, Chedid L, Lefrancier P, Bernard JM (1985) Activation of tumoricidal activity and eradication of experimental metastases by freeze-dried liposomes containing a new lipophilic muramyl dipeptide derivative. Cancer Res 45: 128
Poste G, Kirsh R, Fogler WE, Fidler IJ (1979) Activation of tumoricidal properties in mouse macrophages by lymphokines encapsulated in liposomes. Cancer Res 39: 881
Poste G, Bucana C, Raz A, Bugelski P, Kirsh R, Fidler IJ (1982) Analysis of the fate of systemically administered liposomes and implications for their use in drug delivery. Cancer Res 42: 1412
Poste G, Kirsh R, Bugelski P (1984) Liposomes as a drug delivery system in cancer therapy. In: Sunkara P (ed) Novel approaches to cancer chemotherapy. Academic Press, New York, p 323
Raz A, Fogler WE, Fidler IJ (1979) The effects of experimental conditions on the expression of in vitro mediated tumor cytotoxicity by murine macrophages. Cancer Immunol Immunother 7: 157
Raz A, Bucana C, Fogler WE, Poste G, Fidler IJ (1981) Biochemical, morphological, and ultrastructural studies on the uptake of liposomes by murine macrophages. Cancer Res 41: 487
Sanderson RJ, Shepperdson FT, Vatter AE, Talmadge DW (1977) Isolation and enumeration of peripheral blood monocytes. J Immunol 118: 1409
Schroit AJ, Fidler IJ (1982) Effects of liposome structure and lipid composition on the activation of the tumoricidal properties of macrophages by liposomes containing muramyl dipeptide. Cancer Res 42: 161
Schroit AJ, Hart IR, Madsen J, Fidler IJ (1983) Selective delivery of drugs encapsulated in liposomes: natural targeting to macrophages involved in various disease states. J Biol Response Modif 2: 97
Sone S, Lopez-Berestein G, Fidler IJ (1986) Potentiation of direct cytotoxicity and production of tumor cytolytic factors in human blood monocytes by human recombinant interferon-gamma and muramyl dipeptide derivatives. Cancer Immunol Immunother 2: 93
Sone S, Tandon P, Utsugi T, Ogawara M, Shimizu E, Nii A, Ogura T (1986) Synergism of recombinant interferon gamma with liposome-encapsulated muramyl tripeptide in activation of the tumoricidal properties of human monocytes. Int J Cancer 38: 495
Sone S, Utsugi T, Tandon P, Ogawara M (1986) A dried preparation of liposomes containing muramyl tripeptide phosphatidylethanolamine as a potent activator of human blood monocytes to the antitumor state. Cancer Immunol 22: 191
Talmadge JE, Lenz BF, Klabansky R, Simon R, Riggs C, Guo S, Oldham RK, Fidler IJ (1986) Therapy of autochthonous skin cancers in mice with intravenously injected liposomes containing muramyl-tripeptide. Cancer Res 46: 1160
Turpin J, Hester JP, Hersh EM, Lopez-Berestein G (1986) Centrifugal elutriation as a method for isolation of large numbers of functionally intact human peripheral blood monocytes. J Clin Apheresis 3: 11
van Hoogevest P, Fankhauser P (1989) An industrial liposomal dosage form for muramyl-tripeptide-phosphatidylethanolamine (MTP-PE). In: Lopez-Berestein G, Fidler IJ (eds) Liposomes in the therapy of infectious diseases and cancer. Liss, New York, p 453
Yam LT, Li CY, Crosby WH (1971) Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol 55: 283
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Utsugi, T., Nii, A., Fan, D. et al. Comparative efficacy of liposomes containing synthetic bacterial cell wall analogues for tumoricidal activation of monocytes and macrophages. Cancer Immunol Immunother 33, 285–292 (1991). https://doi.org/10.1007/BF01756592
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DOI: https://doi.org/10.1007/BF01756592