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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1989 Aug 1;170(2):511–526. doi: 10.1084/jem.170.2.511

Antibody-dependent antitumor cytotoxicity by human monocytes cultured with recombinant macrophage colony-stimulating factor. Induction of efficient antibody-mediated antitumor cytotoxicity not detected by isotope release assays

PMCID: PMC2189400  PMID: 2526848

Abstract

Macrophage colony-stimulating factor (M-CSF) is known to stimulate proliferation of monocyte/macrophage progenitors and enhance in vitro antitumor cytotoxicity by murine macrophages. In this paper we have shown that recombinant human M-CSF causes human peripheral blood monocytes to differentiate in culture into metabolically active macrophage-like cells. These cells mediate very efficient antibody- dependent cellular cytotoxicity (ADCC) against human melanoma and neuroblastoma cell lines in the presence of two murine IgG3 mAbs (3F8 and R24). They also mediate antibody-independent cytotoxicity (or cytostasis) to a lesser extent. Human serum had an inconsistent effect on ADCC, but often induced similar high levels of ADCC. Cytotoxicity was measured using a novel ELISA to detect surviving tumor cells after ADCC. Two conventional isotope-release assays (51Cr and [3H]TdR) underestimated or entirely failed to detect ADCC by M-CSF-activated monocytes. Optimal activation occurred with 100-300 U/ml of M-CSF, and required 9-11 d for completion. Most of the M-CSF cultured monocytes expressed the low-affinity Fc receptor (CD16). ADCC by cells of the monocyte/macrophage lineage using murine IgG3 mAbs may have significance for the immunotherapy of human malignancies.

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Selected References

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  1. Adams D. O., Hall T., Steplewski Z., Koprowski H. Tumors undergoing rejection induced by monoclonal antibodies of the IgG2a isotype contain increased numbers of macrophages activated for a distinctive form of antibody-dependent cytolysis. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3506–3510. doi: 10.1073/pnas.81.11.3506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ampel N. M., Wing E. J., Waheed A., Shadduck R. K. Stimulatory effects of purified macrophage colony-stimulating factor on murine resident peritoneal macrophages. Cell Immunol. 1986 Feb;97(2):344–356. doi: 10.1016/0008-8749(86)90405-3. [DOI] [PubMed] [Google Scholar]
  3. Bartocci A., Mastrogiannis D. S., Migliorati G., Stockert R. J., Wolkoff A. W., Stanley E. R. Macrophages specifically regulate the concentration of their own growth factor in the circulation. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6179–6183. doi: 10.1073/pnas.84.17.6179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Becker S., Warren M. K., Haskill S. Colony-stimulating factor-induced monocyte survival and differentiation into macrophages in serum-free cultures. J Immunol. 1987 Dec 1;139(11):3703–3709. [PubMed] [Google Scholar]
  5. Calafat J., Janssen H., Hekman A. Mouse monoclonal antibodies direct phagocytosis of tumor cells by human monocytes. Leuk Res. 1986;10(11):1347–1351. doi: 10.1016/0145-2126(86)90344-9. [DOI] [PubMed] [Google Scholar]
  6. Chen B. D., Mueller M., Chou T. H. Role of granulocyte/macrophage colony-stimulating factor in the regulation of murine alveolar macrophage proliferation and differentiation. J Immunol. 1988 Jul 1;141(1):139–144. [PubMed] [Google Scholar]
  7. Cheresh D. A., Pierschbacher M. D., Herzig M. A., Mujoo K. Disialogangliosides GD2 and GD3 are involved in the attachment of human melanoma and neuroblastoma cells to extracellular matrix proteins. J Cell Biol. 1986 Mar;102(3):688–696. doi: 10.1083/jcb.102.3.688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cheung N. K., Lazarus H., Miraldi F. D., Abramowsky C. R., Kallick S., Saarinen U. M., Spitzer T., Strandjord S. E., Coccia P. F., Berger N. A. Ganglioside GD2 specific monoclonal antibody 3F8: a phase I study in patients with neuroblastoma and malignant melanoma. J Clin Oncol. 1987 Sep;5(9):1430–1440. doi: 10.1200/JCO.1987.5.9.1430. [DOI] [PubMed] [Google Scholar]
  9. Cheung N. K., Saarinen U. M., Neely J. E., Landmeier B., Donovan D., Coccia P. F. Monoclonal antibodies to a glycolipid antigen on human neuroblastoma cells. Cancer Res. 1985 Jun;45(6):2642–2649. [PubMed] [Google Scholar]
  10. Cheung N. K., Walter E. I., Smith-Mensah W. H., Ratnoff W. D., Tykocinski M. L., Medof M. E. Decay-accelerating factor protects human tumor cells from complement-mediated cytotoxicity in vitro. J Clin Invest. 1988 Apr;81(4):1122–1128. doi: 10.1172/JCI113426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Clarkson S. B., Ory P. A. CD16. Developmentally regulated IgG Fc receptors on cultured human monocytes. J Exp Med. 1988 Feb 1;167(2):408–420. doi: 10.1084/jem.167.2.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Eliason J. F. Granulocyte-macrophage colony formation in serum-free culture: effects of purified colony-stimulating factors and modulation by hydrocortisone. J Cell Physiol. 1986 Aug;128(2):231–238. doi: 10.1002/jcp.1041280214. [DOI] [PubMed] [Google Scholar]
  13. Fidler I. J. Macrophages and metastasis--a biological approach to cancer therapy. Cancer Res. 1985 Oct;45(10):4714–4726. [PubMed] [Google Scholar]
  14. Fleit H. B., Wright S. D., Unkeless J. C. Human neutrophil Fc gamma receptor distribution and structure. Proc Natl Acad Sci U S A. 1982 May;79(10):3275–3279. doi: 10.1073/pnas.79.10.3275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gardner C. R., Wasserman A. J., Laskin D. L. Differential sensitivity of tumor targets to liver macrophage-mediated cytotoxicity. Cancer Res. 1987 Dec 15;47(24 Pt 1):6686–6691. [PubMed] [Google Scholar]
  16. Gauci C. L., Alexander P. The macrophage content of some human tumours. Cancer Lett. 1975 Sep;1(1):29–32. doi: 10.1016/s0304-3835(75)94826-0. [DOI] [PubMed] [Google Scholar]
  17. Gmelig-Meyling F., Waldmann T. A. Separation of human blood monocytes and lymphocytes on a continuous Percoll gradient. J Immunol Methods. 1980;33(1):1–9. doi: 10.1016/0022-1759(80)90077-0. [DOI] [PubMed] [Google Scholar]
  18. Grabstein K. H., Urdal D. L., Tushinski R. J., Mochizuki D. Y., Price V. L., Cantrell M. A., Gillis S., Conlon P. J. Induction of macrophage tumoricidal activity by granulocyte-macrophage colony-stimulating factor. Science. 1986 Apr 25;232(4749):506–508. doi: 10.1126/science.3083507. [DOI] [PubMed] [Google Scholar]
  19. Herlyn D., Herlyn M., Steplewski Z., Koprowski H. Monoclonal anti-human tumor antibodies of six isotypes in cytotoxic reactions with human and murine effector cells. Cell Immunol. 1985 Apr 15;92(1):105–114. doi: 10.1016/0008-8749(85)90068-1. [DOI] [PubMed] [Google Scholar]
  20. Johnson W. D., Jr, Mei B., Cohn Z. A. The separation, long-term cultivation, and maturation of the human monocyte. J Exp Med. 1977 Dec 1;146(6):1613–1626. doi: 10.1084/jem.146.6.1613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Johnson W. J., Bolognesi D. P., Adams D. O. Antibody-dependent cytolysis (ADCC) of tumor cells by activated murine macrophages is a two-step process: quantification of target binding and subsequent target lysis. Cell Immunol. 1984 Jan;83(1):170–180. doi: 10.1016/0008-8749(84)90236-3. [DOI] [PubMed] [Google Scholar]
  22. Johnson W. J., Steplewski Z., Matthews T. J., Hamilton T. A., Koprowski H., Adams D. O. Cytolytic interactions between murine macrophages, tumor cells, and monoclonal antibodies: characterization of lytic conditions and requirements for effector activation. J Immunol. 1986 Jun 15;136(12):4704–4713. [PubMed] [Google Scholar]
  23. Kilbourn R. G., Klostergaard J., Lopez-Berestein G. Activated macrophages secrete a soluble factor that inhibits mitochondrial respiration of tumor cells. J Immunol. 1984 Nov;133(5):2577–2581. [PubMed] [Google Scholar]
  24. Klostergaard J. Role of tumor necrosis factor in monocyte/macrophage tumor cytotoxicity in vitro. Nat Immun Cell Growth Regul. 1987;6(4):161–166. [PubMed] [Google Scholar]
  25. Masui H., Moroyama T., Mendelsohn J. Mechanism of antitumor activity in mice for anti-epidermal growth factor receptor monoclonal antibodies with different isotypes. Cancer Res. 1986 Nov;46(11):5592–5598. [PubMed] [Google Scholar]
  26. McBride W. H. Phenotype and functions of intratumoral macrophages. Biochim Biophys Acta. 1986 Aug 5;865(1):27–41. doi: 10.1016/0304-419x(86)90011-9. [DOI] [PubMed] [Google Scholar]
  27. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  28. Munn D. H., Cheung N. K. Interleukin-2 enhancement of monoclonal antibody-mediated cellular cytotoxicity against human melanoma. Cancer Res. 1987 Dec 15;47(24 Pt 1):6600–6605. [PubMed] [Google Scholar]
  29. Musson R. A. Human serum induces maturation of human monocytes in vitro. Changes in cytolytic activity, intracellular lysosomal enzymes, and nonspecific esterase activity. Am J Pathol. 1983 Jun;111(3):331–340. [PMC free article] [PubMed] [Google Scholar]
  30. Nakagawara A., Nathan C. F., Cohn Z. A. Hydrogen peroxide metabolism in human monocytes during differentiation in vitro. J Clin Invest. 1981 Nov;68(5):1243–1252. doi: 10.1172/JCI110370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Nakoinz I., Ralph P. Stimulation of macrophage antibody-dependent killing of tumor targets by recombinant lymphokine factors and M-CSF. Cell Immunol. 1988 Oct 15;116(2):331–340. doi: 10.1016/0008-8749(88)90235-3. [DOI] [PubMed] [Google Scholar]
  32. Perussia B., Trinchieri G., Jackson A., Warner N. L., Faust J., Rumpold H., Kraft D., Lanier L. L. The Fc receptor for IgG on human natural killer cells: phenotypic, functional, and comparative studies with monoclonal antibodies. J Immunol. 1984 Jul;133(1):180–189. [PubMed] [Google Scholar]
  33. Ralph P., Nakoinz I. Stimulation of macrophage tumoricidal activity by the growth and differentiation factor CSF-1. Cell Immunol. 1987 Apr 1;105(2):270–279. doi: 10.1016/0008-8749(87)90076-1. [DOI] [PubMed] [Google Scholar]
  34. Ralph P., Warren M. K., Nakoinz I., Lee M. T., Brindley L., Sampson-Johannes A., Kawasaki E. S., Ladner M. B., Strickler J. E., Boosman A. Biological properties and molecular biology of the human macrophage growth factor, CSF-1. Immunobiology. 1986 Sep;172(3-5):194–204. doi: 10.1016/S0171-2985(86)80099-7. [DOI] [PubMed] [Google Scholar]
  35. Saarinen U. M., Coccia P. F., Gerson S. L., Pelley R., Cheung N. K. Eradication of neuroblastoma cells in vitro by monoclonal antibody and human complement: method for purging autologous bone marrow. Cancer Res. 1985 Nov;45(11 Pt 2):5969–5975. [PubMed] [Google Scholar]
  36. Sampson-Johannes A., Carlino J. A. Enhancement of human monocyte tumoricidal activity by recombinant M-CSF. J Immunol. 1988 Nov 15;141(10):3680–3686. [PubMed] [Google Scholar]
  37. Simmons D., Seed B. The Fc gamma receptor of natural killer cells is a phospholipid-linked membrane protein. Nature. 1988 Jun 9;333(6173):568–570. doi: 10.1038/333568a0. [DOI] [PubMed] [Google Scholar]
  38. Steplewski Z., Lubeck M. D., Koprowski H. Human macrophages armed with murine immunoglobulin G2a antibodies to tumors destroy human cancer cells. Science. 1983 Aug 26;221(4613):865–867. doi: 10.1126/science.6879183. [DOI] [PubMed] [Google Scholar]
  39. Thurin J., Thurin M., Kimoto Y., Herlyn M., Lubeck M. D., Elder D. E., Smereczynska M., Karlsson K. A., Clark W. M., Jr, Steplewski Z. Monoclonal antibody-defined correlations in melanoma between levels of GD2 and GD3 antigens and antibody-mediated cytotoxicity. Cancer Res. 1987 Mar 1;47(5):1229–1233. [PubMed] [Google Scholar]
  40. Tushinski R. J., Oliver I. T., Guilbert L. J., Tynan P. W., Warner J. R., Stanley E. R. Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. Cell. 1982 Jan;28(1):71–81. doi: 10.1016/0092-8674(82)90376-2. [DOI] [PubMed] [Google Scholar]
  41. Warren M. K., Ralph P. Macrophage growth factor CSF-1 stimulates human monocyte production of interferon, tumor necrosis factor, and colony stimulating activity. J Immunol. 1986 Oct 1;137(7):2281–2285. [PubMed] [Google Scholar]
  42. Wing E. J., Ampel N. M., Waheed A., Shadduck R. K. Macrophage colony-stimulating factor (M-CSF) enhances the capacity of murine macrophages to secrete oxygen reduction products. J Immunol. 1985 Sep;135(3):2052–2056. [PubMed] [Google Scholar]
  43. Wong G. G., Temple P. A., Leary A. C., Witek-Giannotti J. S., Yang Y. C., Ciarletta A. B., Chung M., Murtha P., Kriz R., Kaufman R. J. Human CSF-1: molecular cloning and expression of 4-kb cDNA encoding the human urinary protein. Science. 1987 Mar 20;235(4795):1504–1508. doi: 10.1126/science.3493529. [DOI] [PubMed] [Google Scholar]

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