Abstract
The metastatic spread of malignant tumors to form metastases at other sites in the body remains the principal cause of failure in the treatment of neoplastic disease1. Several factors are responsible for this unfortunate situation. First, metastases are frequently too small to be detected at the time the primary tumor is removed. Second, widespread dissemination of metastases often takes place before symptoms of metastatic disease occur. Third, the anatomic location of many metastatic lesions renders them inaccessible to surgical removal and/or limits the effective dose of therapeutic agents that reach metastases. The final, and most formidable, problem concerns emergence of metastatic lesions that are resistant to conventional therapy. Recent work suggests that metastases arise from non-random spread of specialized subpopulations of cells within the primary tumor and that the responsiveness of these metastatic subpopulations to therapy may not only differ from that of non-metastatic tumor cells in the primary tumor but may also vary significantly between the tumor cell subpopulations present in individual metastases within the same patient (review, 2). The depressing implication of this marked heterogeneity in the response of malignant cells to chemotherapy and other therapeutic modalities is that the only successful approach to the therapy of metastases will be one that circumvents the problem of cellular diversity between tumor cells in primary and metastatic lesions, and between different metastatic foci.
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References
G. Poste and I.J. Fidler, The pathogenesis of cancer metastases, Nature, 283: 139 (1980).
I.J. Fidler and M.L. Kripke, Biological variability within murine neoplasms, Antibiot. Chemother. 28: 123 (1980).
I.J. Fidler, Recognition and destruction of target cells by tumoricidal macrophages, Isr. J. Med. Sci. 14: 177 (1978).
R.S. Kerbel, Implications of immunological heterogeneity of tumours, Nature 280: 358 (1979).
E. Den Otter, F.J. Dullens Hub, H. Van Lovern and E. Pels, Antitumor effects of macrophages injected into animals: a review, in: “The Macrophage and Cancer,” K. James, B. McBride and A. Stuart, eds., Econoprint, Edinburgh, (1977).
I.J. Fidler, Inhibition of pulmonary metastasis by intravenous injection of specifically activated macrophages, Cancer Res. 34: 1074 (1977).
L.A. Liotta, C. Gattozzi, J. Kleinerman and G. Saidel, Reduction of tumor-cell entry into vessels by BCG-activated macrophages, Brit. J. Cancer 36: 639 (1977).
I.J. Fidler and G. Poste, Macrophage destruction of micro-metastases, in: “Manual of Macrophage Methodology,” H.B. Herscowitz, H.J. Holden, J.A. Bellanti and A. Ghaffar, eds., Marcel Dekker, New York (1981).
I.J. Fidler, Z. Barnes, W.E. Fogler, R. Kirsh, P. Bugelski and G. Poste, Evidence for the involvement of macrophages in the eradication of established metastases following intravenous injection of liposomes containing macrophage activators, Cancer Res. - submitted.
S.W. Russell, G.Y. Gillespie and J.L. Pace, Evidence for mononuclear phagocytes in solid neoplasms and appraisal of the nonspecific cytotoxic capabilities, in: “In Situ Expression of Tumor Immunity,” I. P. Witz and M.G. Hanna, eds., Plenum, New York (1980).
A.C. Allison, Mode of action of immunological adjuvants, J. Reticuloendothel. Soc. 26: 619 (1979).
I.J. Fidler and A. Raz, The induction of tumoricidal capacities in mouse and rat macrophages by lymphokines, in: “Lymphokines,” E. Pick, ed., Vol. 3, Academic Press, New York, (1981).
B.W. Papermaster, O.A. Holterman, E. Klein, I. Djerassi, D. Rosner, T. Dao and J.J. Costanzi, Preliminary observations on tumor regressions induced by local administration of a lymphoid-cell culture supernatant fraction in patients with cutaneous metastatic lesions, Clin. Immunol. Immunopathol. 5: 31 (1976).
S.B. Slavin, J.S. Youngner, J. Nishio and R. Neta, Brief communication: tumor suppression by a lymphokine released into the circulation of mice with delayed hypersensitivity, J. Nat. Cancer Inst. 55: 1233 (1975).
N.E. Adelman, M.G. Hammond, S. Cohen and H.F. Dvorak, Lymphokines as inflammatory mediators, in: “Biology of the Lymphokines,” S. Cohen, E. Pick and J.J. Oppenheim, eds., Academic Press, New York (1979).
G. Poste and R. Kirsh, Rapid decay of tumoricidal activity and loss of responsiveness to lymphokines in inflammatory macrophages, Cancer Res. 39: 2582 (1979).
L. Chedid, F. Audibert and A.G. Johnson, Biological activities of muramyl dipeptide, a synthetic glycopeptide analogous to bacterial immunoregulating agents, Progr. Allergy 25: 63 (1978).
G. Gregoriadis and A.C. Allison, eds., in: “Liposomes in Biology and Medicine,” Wiley Interscience, New York (1980).
T.D. Heath, R.T. Fraley and D. Papahadjopoulos, Antibody targeting of liposomes - cell specificity obtained by conjugation of F(AB)2 to vesicle surface, Science, 210: 539 (1980).
L.D. Leserman, J.N. Weinstein, R. Blumenthal and W.D. Terry, Receptor mediated endocytosis of antibody-opsonized liposomes by tumor cells, Proc. Nat. Acad. Sci. USA, 77: 4089 (1980).
G. Gregoriadis and D. Neerunjun, Homing of liposomes to target cells, Biochem. Biophys, Res. Commun. 65: 537 (1975).
G. Poste, R. Kirsh and I.J. Fidler, Cell surface receptors for lymphokines. I. The possible role of glycolipids as receptors for macrophage migration inhibitory factor (MIF) and macrophage activation factor (MAF), Cell Innnunol. 44: 71 (1979).
G. Poste, R. Kirsh, W.E. Fogler and I.J. Fidler, Activation of tumoricidal properties in mouse macrophages by lymphokines encapsulated in liposomes, Cancer Res. 39: 881 (1979).
I.J. Fidler, S. Sone, W.E. Fogler and Z. Barnes, Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide, Proc. Nat. Acad. Sci. USA, 78: 1680 (1981).
I.J. Fidler, A. Raz, W.E. Fogler, R. Kirsh, P. Bugelski and G. Poste, Design of liposomes to improve delivery of macrophage-augmenting agents to alveolar macrophages, Cancer Res. 40: 4460 (1980).
I.J. Fidler, I.R. Hart, A. Raz, W.E. Fogler, R. Kirsh and G. Poste, Activation of tumoricidal properties in macrophages by liposome-encapsulated lymphokines: in vivo studies, in: “Liposomes and Immunobiology,” B.H. Tom and H. Six, eds., Elsevier, New York (1980).
S. Sone, G. Poste and I.J. Fidler, Rat alveolar macrophages are susceptible to activation by free and liposome-encapsulated lymphokines, J. Immunol. 124: 2197 (1980).
G. Poste, C. Bucana, A. Raz, R. Kirsh, P. Bugelski and I.J. Fidler, The behaviour of intravenously inoculated liposomes in the microcirculation: implications for liposome targeting and drug delivery, Cancer Res. - submitted.
G.P. Velo and W.G. Spector, The origin and turnover of alveolar macrophages in experimental pneumonia, J. Pathol. 109: 7 (1973).
E.D. Thomas, R.E. Ramberg, G.E. Sale, R.S. Sparkes and D.W. Golde, Direct evidence for a bone marrow origin of the alveolar macrophage in man, Science, 192: 1016 (1976).
K.J. Johnson, P.A. Ward, G. Striker and R. Kunkel, A study of the origin of pulmonary macrophages using the Chediak-Higashi marker, Am. J. Pathol. 101: 365 (1980).
A. Blusse van Ould Alblas and R. Van Furth, Origin, kinetics and characteristics of pulmonary macrophages in the normal steady state, J. Exp. Med. 149: 1504 (1979).
I.R. Hart, Selection and characterization of an invasive variant of the B16 melanoma, Am. J. Pathol. 97: 587 (1979).
I.J. Fidler, Therapy of spontaneous metastases by intravenous injection of liposomes containing lymphokines, Science 208: 1469 (1980).
M. Parant, Biological properties of a new synthetic adjuvant, muramyl dipeptide (MDP), Semin. Immunopathol. 2: 101 (1979).
D.P. Griswold, Jr., Consideration of subcutaneously implanted B16 melanoma as a screening model for potential anticancer agents, Cancer Chemotherap. Rep. 3: 315 (1972).
M. Aalto, M. Potila and E. Kulonen, The effect of silica-treated macrophages on the synthesis of collagen and other proteins in vitro, Exp. Cell Res. 97: 193 (1976).
C.F. Brosnan, M.B. Bornstein and B.R. Bloom, The effects of macrophage depletion on the clinical and pathological expression of experimental allergic encephalomyelitis, J. Immunol. 126: 614 (1981).
P.J. Cantanzaro, H.J. Schwartz and R.C. Graham, Jr., Spectrum and possible mechanism of carrageenan cytotoxicity, Am. J. Pathol. 64: 387 (1971).
D.G. Hopper, M.V. Pimm and R.W. Baldwin, Silica abrogation of mycobacterial adjuvant contact suppression of tumor growth in rats and athymic mice, Cancer Immunol. Immunother. 1: 143 (1976).
R. Keller, Promotion of tumor growth in vivo by anti-macrophage agents, J. Nat. Cancer Inst. 57: 1355 (1976).
M.H. Levy and E.F. Wheelock, Effects of intravenous silica on immune and non-immune functions of the murine host, J. Immunol. 115: 41 (1975).
A.W. Thomson, N. Cruickshank and E.F. Fowler, Fc receptor-bearing and phagocytic cells in syngeneic tumors of corynebacterium-parvum treated and carrageenan treated mice, Brit. J. Cancer 39: 598 (1979).
S.D. Miller and A. Zarkower, Alterations of murine immunological responses after silica dust inhalation, J. Immunol. 113: 1533 (1974).
E. Lotzova, C. parvum-mediated suppression of the phenomenon of natural killing and its analysis, in: “Natural Cell-Mediated Immunity Against Tumors,” R.B. Herberman, ed., Plenum, New York (1980).
G. Poste, unpublished observations.
I.J. Fidler, J. Immunol. - in press (1981).
S. Sone and I.J. Fidler, In vitro activation of tumoricidal properties in rat alveolar macrophages by synthetic muramyl dipeptide encapsulated in liposomes, Cell Immunol. 57: 42 (1981).
I.R. Hart, W.E. Fogler, G. Poste and I.J. Fidler, Toxicity studies of liposome-encapsulated imetunomodulators administered intravenously to dogs and mice, Cancer Immunol Immunother. 10: 157 (1981).
S.A. Eccles, Macrophages and cancer, in: “Immunological Aspects of Cancer,” J.E. Castro, ed., Univ. Park Press, Baltimore (1978).
M.J. Berendt and R.J. North, T-cell mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor, J. Exp. Med. 151: 69 (1980).
L.P. Ruco and M.S. Meltzer, Macrophage activation for tumor cytotoxicity: increased lymphokine responsiveness of peritoneal macrophages during acute inflammation, J. Immunol. 120: 1054 (1978).
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Poste, G., Bucana, C., Fidler, I.J. (1982). Stimulation of Host Response Against Metastatic Tumors by Liposome-Encapsulated Immunomodulators. In: Gregoriadis, G., Senior, J., Trouet, A. (eds) Targeting of Drugs. NATO Advanced Study Institutes Series, vol 47. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4241-0_16
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