Biological response modifier having cell differentiation-inducti

Details Biological response modifier having cell differentiation-inducti Biological response modifier having cell differentiation-inducti

1984-11-07

1988-07-26

Tarcza, John

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Enzymatic production of a protein or polypeptide

530351, C12P 2100, C07K 302, A61K 3702

Patent

active

047600217

ABSTRACT:
There is provided a proteinaceous biological response modifier having the following properties: (a) molecular weight: 35,000 to 65,000; (b) isoelectric point: 5.0 to 6.1; (c) physiological action on human leukemia cells: to induce human leukemia to differentiate into macrophage-like cells; (d) physiological action on myeloid leukemia cells from mice: to induce myeloid leukemia cells from mice to differentiate into macrophage-like cells; (e) affinity to Concanavalin A Sepharose: not adsorbed; (f) affinity to Blue Sepharose Resin: not adsorbed; (g) pH-stability and thermostability: substantially not inactivated at pH 2 to 10, at 2.degree. C. for 6 hours; not inactivated at 56.degree. C. for 60 minutes; but inactivated by 30% at 70.degree. C. for 60 minutes; (h) sensitivity to enzymes: not inactivated by deoxyribonuclease; not inactivated by glycosidase; and inactivated by protease; (i) flow cytometry analysis: to concentrate cell division cycle of human leukemia cells to G.sub.0 /G.sub.1 phase. There is also provided a process for the production of the proteinaceous biological response modifier comprising culturing human leukemia cells in a differentiation medium in the presence of a substance capable of inducing the human leukemia cells to differentiate into macrophage-like cells; separating the macrophage-like cells from the culture medium; activating the macrophage-like cells in a production medium by a mitogen to enhance the production of the proteinaceous biological response modifier; and isolating the proteinaceous biological response modifier from the production medium.
The biological response modifier has anti-tumor activity.

REFERENCES:
Rovera et al., "Induction of Differentiation in Human Promyelocytic Leukemia Cells by Tumor Promotors", Science, vol. 204, 25 May 1979, pp. 868-870.
Olsson et al., "Characterization of Mononuclear Cell-Derived Differentiation Inducing Factors for the Human Promyelocytic Cell Line HL-60", JNCI, 67, 6 Dec. 1981, pp. 1225-1230.
Maeda et al., "Characterization of a Differentiation-Stimulating Factor for Mouse Myeloid Leukemia Cells", Gann, 68, Aug. 1977, pp. 435-447.
Vogel et al., "LPS unresponsive Mice as a Model for Analyzing Lymphokine-Induced Maerophage Differentiation in Vitro", Lymphokines 3, E. Pick and M. Landy Eds., Academic Press, New York, 1981, pp. 153-154.
William F. Ganong, "Review of Medical Physiology", Chapter 27, pp. 414-416.
Olsson et al., Cancer Research, 42, 3928-3933 (1982).
Tsuchiya et al., Int. J. Cancer, 26, 171-176 (1980).

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