Skip to main content
SpringerLink
Log in

Circumvention of Neoplastic Heterogeneity by Systemically Activated Macrophages

  • Chapter
Biology and Treatment of Colorectal Cancer Metastasis

Part of the book series: Developments in Oncology ((DION,volume 42))

  • 53 Accesses

Summary

The continuous growth of metastases that are resistant to conventional therapies is the major cause of death from colorectal carcinoma. Recent data indicate that metastases can arise from the nonrandom spread of specialized subpopulations of cells that preexist within the primary tumor, that metastases can be clonal in their origin, that different metastases can originate from different progenitor cells, and that metastatic cells can have an increased rate of spontaneous mutation as compared with benign, nonmetastatic cells. Therefore, the successful therapy of disseminated metastases will have to circumvent the problems of cancer heterogeneity and the development of tumor cell resistance to therapy.

Appropriately activated macrophages can fulfill these demanding criteria. Macrophages obtained from normal donors or from patients with colorectal carcinoma can be activated to become tumoricidal subsequent to endocytosis of phospholipid vesicles (liposomes) containing specific immunomodulators. Macrophages thus activated can recognize and destroy neoplastic cells in vitro or in vivo, while leaving nonneoplastic cells unharmed. Moreover, macrophage destruction of tumor cells is not associated with the development of tumor cell resistance.

The major limitations of many cancer therapies are their lack of selectivity against cancer cells. The ability of tumoricidal human monocytes to distinguish neoplastic from bystander nonneoplastic cells, therefore, presents an attractive possibility for treatment of disseminated cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Fidler IJ, Hart IR: Biological diversity in metastatic neoplasms: Origins and implications. Science 217: 998–1003, 1982.

    Article  PubMed  CAS  Google Scholar 

  2. Poste G, Fidler IJ: The pathogenesis of cancer metastasis. Nature 283: 139–146, 1979.

    Article  Google Scholar 

  3. Fidler IJ, Kripke ML: Metastasis results from preexisting variant cells within a malignant tumor. Science 197: 893–895, 1977.

    Article  PubMed  CAS  Google Scholar 

  4. Talmadge JE, Wolman SR, Fidler IJ: Evidence for the clonal origin of spontaneous metastases. Science 217: 361–363, 1982.

    Article  PubMed  CAS  Google Scholar 

  5. Fidler IJ, Poste G: Macrophage-mediated destruction of malignant tumor cells and new strategies for the therapy of metastatic disease. Springer Semin Immunopathol 5: 161–174, 1982.

    Article  PubMed  CAS  Google Scholar 

  6. Tanaka Y, Schroit A: Insertion of fluorescent phosphatidylserine into the plasma membrane of red blood cells: Recognition by autologous macrophages. J Biol Chem 258: 11335–11343, 1983.

    PubMed  CAS  Google Scholar 

  7. Chedid L, Carein L, Audibert F: Recent developments concerning muramyl dipeptide, a synthetic immunoregulating molecule. J Reticuloendothel Soc 26: 631–1979.

    Google Scholar 

  8. Lederer E: Synthetic immunostimulants derived from the bacterial cell wall. J Med Chem 23: 819–825, 1980.

    Article  PubMed  CAS  Google Scholar 

  9. Fidler IJ, Raz A: The induction of tumoricidal capacities in mouse and rat macrophages by lymphokines. In: E Pick (ed) Lymphokines. Academic Press, New York, 1981, pp. 345–363.

    Google Scholar 

  10. Poste G, Kirsh R, Fidler IJ: Cell surface receptors for lymphokines. Cell Immunol 71–88, 1979.

    Google Scholar 

  11. Bucana C, Hoyer LL, Hobbs B, Breesman S, McDaniel M, Hanna MG Jr: Morphological evidence for the translocation of lysosomal organelles from cytotoxic macrophages into the cytoplasm of tumor target cells. Cancer Res 36: 1976.

    Google Scholar 

  12. Hibbs JB Jr: Discrimination between neoplastic and non-neoplastic cells in vitro by activated macrophages. J Natl Cancer Inst 53: 1487–1492, 1974.

    PubMed  Google Scholar 

  13. Papermaster BW, Gilliand CD, McEntire JE, Rodes ND, Dunn PA: In vivo biological studies with lymphoblastoid lymphokines. In: AL Goldstein and MA Chirigos (eds) Lymphokines and Thymic Hormones: Their Potential Utilization in Cancer Therapeutics. Raven Press, New York, 1981, pp. 289–299.

    Google Scholar 

  14. Papermaster BW, Holtermann OA, Rosner D, Klein E, Dao T, Djerassi I: Regressions produced in breast cancer lesions by a lymphokine fraction from a human lymphoid cell line. Res Commun Pathol Pharmacol 8: 413–416, 1974.

    CAS  Google Scholar 

  15. Salvin SB, Youngner JS, Nishio J, Neta R: Tumor suppression by a lymphokine released into the circulation of mice with delayed hypersensitivity. J Natl Cancer Inst 55: 1233–1236, 1975.

    PubMed  CAS  Google Scholar 

  16. Poste G, Kirsh R, Fogler W, Fidler IJ: Activation of tumoricidal properties in mouse macrophages by lymphokines encapsulated in liposomes. Cancer Res 39: 881–892, 1979.

    PubMed  CAS  Google Scholar 

  17. Poste G, Kirsh R: Rapid decay of tumoricidal activity and loss of responsiveness to lymphokines in inflammatory macrophages. Cancer Res 39: 2582–2590, 1979.

    PubMed  CAS  Google Scholar 

  18. Parant M, Parant F, Chedid L, Yapo A, Petit JF, Lederer E: Fate of the synthetic immunoadjuvant, muramyl dipeptide (14C-labeled) in the mouse. Int J Immunopharmacol 1: 35–41, 1979.

    Article  PubMed  CAS  Google Scholar 

  19. Sone S, Fidler IJ: In vitro activation of tumoricidal properties in rat alveolar macrophages by synthetic muramyl dipeptide encapsulated in liposomes. Cell Immunol 57: 42–50, 1981.

    Article  PubMed  CAS  Google Scholar 

  20. Sone S, Fidler IJ: Synergistic activation by lymphokines and muramyl dipeptide of tumoricidal properties in rat alveolar macrophages. J Immunol 125: 2454–2460, 1980.

    PubMed  CAS  Google Scholar 

  21. Allison AC: Mode of action of immunological adjuvants. J Reticuloendothel Soc 26: 61–630, 1979.

    Google Scholar 

  22. Fidler IJ, Raz A, Fogler WE, Hoyer LC, Poste G: The role of plasma membrane receptors and the kinetics of macrophage activation by lymphokines encapsulated in liposomes. Cancer Res 41: 495–504, 1981.

    PubMed  CAS  Google Scholar 

  23. Fogler WE, Raz A, Fidler IJ: In situ activation of murine macrophages by liposomes containing lymphokines. Cell Immunol 53: 214–219, 1980.

    Article  PubMed  CAS  Google Scholar 

  24. Sone S, Poste G, Fidler IJ: Rat alveolar macrophages are susceptible to activation by free and liposome-encapsulated lymphokines. J Immunol 124: 2197–2201, 1980.

    PubMed  CAS  Google Scholar 

  25. Fidler IJ, Raz A, Fogler WE, Kirsh R, Bugelski P, Poste G: Design of liposomes to improve delivery of macrophage-augmenting agents to alveolar macrophages. Cancer Res 40: 1980.

    Google Scholar 

  26. Fidler IJ, Raz A, Fogler WE, Hoyer LC, Poste G. The role of plasma membrane receptors and the kinetics of macrophage activation by lymphokines encapsulated in liposomes. Cancer Res 41: 495–504, 1980.

    Google Scholar 

  27. Schroit AJ, Fidler IJ: Effects of liposome structure and lipid composition on the activation of the tumoricidal properties of macrophages by liposomes containing muramyl dipeptide. Cancer Res 42: 161–167, 1982.

    PubMed  CAS  Google Scholar 

  28. Fidler IJ: Therapy of spontaneous metastases by intravenous injection of liposomes containing lymphokines. Science 208: 1469–1471, 1980.

    Article  PubMed  CAS  Google Scholar 

  29. Fidler IJ, Sone S, Fogler WE, Barnes ZL: Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide. Proc Natl Acad Sei USA 78: 1680–1684, 1981.

    Article  CAS  Google Scholar 

  30. Fidler IJ, Fogler WE: Activation of tumoricidal properties in macrophages by lymphokines encapsulated in liposomes. Lymphokine Research 1: 73–77, 1982.

    PubMed  CAS  Google Scholar 

  31. Fidler IJ: The in situ induction of tumoricidal activity in alveolar macrophages by liposomes containing muramyl dipeptide is a thymus-independent process. J Immunol 127: 1719–1720, 1981.

    PubMed  CAS  Google Scholar 

  32. Fidler IJ, Schroit AJ: Synergism between lymphokines and muramyl dipeptide encapsulated in liposomes: In situ activation of macrophages and therapy of spontaneous cancer metastases. J Immunol 133: 515–518, 1984.

    PubMed  CAS  Google Scholar 

  33. Kleinerman ES, Schroit AJ, Fogler WE, Fidler IJ: Tumoricidal activity of human monocytes activated in vitro by free and liposome-encapsulated human lymphokines. J Clin Invest 72: 1–12, 1983.

    Article  Google Scholar 

  34. Kleinerman ES, Fidier IJ: Production and utilization of human lymphokines containing macrophage-activating factor (MAF) activity. Lymphokine Research 2: 7–12, 1983.

    PubMed  CAS  Google Scholar 

  35. Kleinerman, ES, Erickson KL, Schroit AJ, Foler WE, Fidler IJ: Activation of tumoricidal properties in human blood monocytes by liposomes containing lipophilic muramyl tripeptide. Cancer Res 43: 2010–2014, 1983.

    PubMed  CAS  Google Scholar 

  36. Fidler IJ, Kleinerman ES: Lymphokine-activated human blood monocytes destroy tumor cells but not normal cells under cocultivation conditions. J Clin Oncol 2: 937–943, 1984.

    PubMed  CAS  Google Scholar 

  37. Bucana CD, Hoyer LC, Schroit A J, Kleinerman E, Fidler IJ: Ultrastructural studies of the interaction between liposome-activated human blood monocytes and allogeneic tumor cells in vitro. Am J Pathol 112: 101–111, 1983.

    PubMed  CAS  Google Scholar 

  38. Hibbs JB Jr: Heterocytolysis by macrophages activated by Bacillus Calmette- Guerin: Lysosome exocytosis into tumor cells. Science 184: [974.

    Google Scholar 

  39. Fidler IJ: Recognition and destruction of target cells by tumoricidal macrophages. Isr J Med Sci 14: 177–191, 1978.

    PubMed  CAS  Google Scholar 

  40. Schroit AJ, Hart IR, Madsen J, Fidler IJ: Selective delivery of drugs encapsulated in liposomes: Natural targeting to macrophages involved in various disease states. J Biol Response Mod 2: 97–100, 1983.

    PubMed  CAS  Google Scholar 

  41. Fidler IJ: The in situ induction of tumoricidal activity in alveolar macrophages by liposomes containing muramyl dipeptide is a thymus-independent process. J Immunol 127: 1719–1720, 1981.

    PubMed  CAS  Google Scholar 

  42. Hart IR, Fogler WE, Poste G, Fidler IJ: Toxicity studies of liposome-enapsulated immunomodulators administered intravenously into dogs and mice. Cancer Immunol Immunother 10: 157–166, 1981.

    Article  CAS  Google Scholar 

  43. Griswold DP Jr: Consideration of the subcutaneously implanted B16 melanoma as a screening model for potential anticancer agents. Cancer Chemotherapy Reports 3: 315–323, 1972.

    Google Scholar 

  44. Deodhar SD, Barna BP, Edinger M, Chiang T: Inhibition of lung metastases by liposomal immunotherapy in a murine fibrosarcoma model. J Biol Response Mod 1: 27–34, 1982.

    Google Scholar 

  45. Lopez-Berestein G, Milas L, Hunter N, Mehta K, Eppstein D, Van der Pas MA, Mathews TR, Hersh EM: Prophylaxis and treatment of experimental lung metastases in mice after treatment with liposome encapsulated 6-O-steroyl-N- acetyl muramyl-L-aminobutyryl-D-isoglutamine.. Clin Exp Metastasis 2: 366–367, 1984.

    Article  Google Scholar 

  46. Fidler IJ, Barnes Z, Fogler WE, Kirsh R, Bugelski P, Poste G: Involvement of macrophages in the eradication of established metastases following intravenous injection of liposomes containing macrophage activators. Cancer Res 42: 496–501, 1982.

    PubMed  CAS  Google Scholar 

  47. Key ME, Talmadge JE, Fogler WE, Bucana C, Fidler IJ: Isolation of tumoricidal macrophages from lung melanoma metastases of mice treated systemically with liposomes containing a lipophilic derivative of muramyl dipeptide. J Natl Cancer Inst 69: 1189–1198, 1982.

    CAS  Google Scholar 

Download references

Authors
  1. Isaiah J. Fidler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Milburn Jessup
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eugenie S. Kleinerman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William E. Fogler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Amitabha Mazumder
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. M. D. Anderson Hospital and Tumor Institute Texas Medical Center, The University of Texas System Cancer Center, Houston, Texas, USA

    Anthony J. Mastromarino Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1986 Martinus Nijhoff Publishing, Boston

About this chapter

Cite this chapter

Fidler, I.J., Jessup, J.M., Kleinerman, E.S., Fogler, W.E., Mazumder, A. (1986). Circumvention of Neoplastic Heterogeneity by Systemically Activated Macrophages. In: Mastromarino, A.J. (eds) Biology and Treatment of Colorectal Cancer Metastasis. Developments in Oncology, vol 42. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2301-3_25

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-2301-3_25

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-9417-7

  • Online ISBN: 978-1-4613-2301-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation