Biological and antitumor effects of recombinant human macrophage colony-stimulating factor in mice

Steven N. Bock, Robert B. Cameron, Peter Kragel, James J. Mulé, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

The administration of recombinant human macrophage colony-stimulating factor (M-CSF) i.p. in doses of 25 or 100 μg twice daily for 5 consecutive days to non-tumor-bearing C57BL/6 mice resulted in a dose-dependent infiltration of mononuclear cells in the livers but not the lungs of these treated animals. Immunohistochemical examination of fixed liver tissue with the murine macrophage-specific monoclonal antibody, F4/80, revealed a >5-fold increase in the number of hepatic macrophages. Quantification of F4/80-positive cells in a mononuclear single cell suspension derived from liver revealed a >25-fold expansion in the number of hepatic macrophages compared to control mice. These cells were then tested in 18-h 51Cr release assays for tumoricidal activity, after an 18-h incubation with or without γ-interferon, against cultured P815 targets. Significant tumor cell lysis by these liver-associated mononuclear cells occurred, which was enhanced by γ-interferon preincubation. The systemic administration of M-CSF alone at high dose had no antitumor impact in vivo against 3-day pulmonary metastases from the MCA-203 sarcoma and B16 melanoma or hepatic metastases from the B16 melanoma or MCA-105, -203, or -207 sarcomas. Although the systemic administration of M-CSF in combination with tumor-specific monoclonal antibody had no effect on 3-day pulmonary metastases from the B16 melanoma, significant reductions in liver metastases were seen. These murine studies demonstrate the biological activity of recombinant human M-CSF in vivo and suggest that the administration of this cytokine in combination with specific monoclonal antibody may be useful in the treatment of patients with metastatic disease at sites of monocyte/macrophage accumulation.

Original languageEnglish (US)
Pages (from-to)2649-2654
Number of pages6
JournalCancer Research
Volume51
Issue number10
StatePublished - May 15 1991
Externally publishedYes

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Macrophage Colony-Stimulating Factor
Liver
Experimental Melanomas
Macrophages
Neoplasm Metastasis
Monoclonal Antibodies
Sarcoma
Lung
Interferons
Inbred C57BL Mouse
Human Activities
Monocytes
Neoplasms
Suspensions
Cytokines

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bock, S. N., Cameron, R. B., Kragel, P., Mulé, J. J., & Rosenberg, S. A. (1991). Biological and antitumor effects of recombinant human macrophage colony-stimulating factor in mice. Cancer Research, 51(10), 2649-2654.

Biological and antitumor effects of recombinant human macrophage colony-stimulating factor in mice. / Bock, Steven N.; Cameron, Robert B.; Kragel, Peter; Mulé, James J.; Rosenberg, Steven A.

In: Cancer Research, Vol. 51, No. 10, 15.05.1991, p. 2649-2654.

Research output: Contribution to journalArticle

Bock, SN, Cameron, RB, Kragel, P, Mulé, JJ & Rosenberg, SA 1991, 'Biological and antitumor effects of recombinant human macrophage colony-stimulating factor in mice', Cancer Research, vol. 51, no. 10, pp. 2649-2654.
Bock SN, Cameron RB, Kragel P, Mulé JJ, Rosenberg SA. Biological and antitumor effects of recombinant human macrophage colony-stimulating factor in mice. Cancer Research. 1991 May 15;51(10):2649-2654.
Bock, Steven N. ; Cameron, Robert B. ; Kragel, Peter ; Mulé, James J. ; Rosenberg, Steven A. / Biological and antitumor effects of recombinant human macrophage colony-stimulating factor in mice. In: Cancer Research. 1991 ; Vol. 51, No. 10. pp. 2649-2654.
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