Drug – bio-affecting and body treating compositions – Lymphokine – Interleukin
Patent
1991-12-30
1993-09-21
Wityshyn, Michael G.
Drug, bio-affecting and body treating compositions
Lymphokine
Interleukin
530351, 514 8, 514 12, 514 21, 435975, A61K 3704, A61K 3900, A61K 3702
Patent
active
052466990
DESCRIPTION:
BRIEF SUMMARY
The invention concerns the use of IgE-binding factor (IgE-bf) for the stimulation of the maturation, i.e. of the differentiation and proliferation, of myeloid precursor cells in context with interleukin-1 (IL-1). The invention further concerns a pharmaceutical preparation comprising IgE-bf either alone or in combination with IL-1 for the treatment or prevention of diseases by stimulating the maturation of myeloid precursor cells.
BACKGROUND OF THE INVENTION
Blood contains a heterogeneous population of cells which can be divided into different lineages, i.e. into cells of the myeloid and the lymphoid lineages. The lymphoid cell population consists of B- and T-lymphocytes and their precursors while the myeloid population comprises monocytes, macrophages, erythrocytes, platelets and different types of granulocytes as well as their progenitors.
The whole heterogeneous population of blood cells originates from a common set of pluripotent stem cells in the bone marrow. The production of the blood cells, i.e. the hematopoiesis, is a strongly regulated complex process. The pathway of blood cell development is furcated. Starting from a pluripotent stem cell, more and more specialized progenitor cells and finally the fully developed blood cells occur in a stepwise process. The stepwise differentiation of the progenitor cells can be monitored by the occurence of certain patterns of surface markers which are specific for the different cell types. The replication and differentiation of the cells is dependent on the continuous supply of specific protein factors which act as regulators of hematopoiesis. (For review see S. C. Clark and R. Kamen, Science 236: 1229-37, 1987)
The progenitor cell of the whole myeloid lineage which is identified in in vitro culture systems is a so called CFU-GEMM (colony-forming unit granulocyte-erythrocyte-monocyte-megakaryocyte). It gives rise to the myeloid precursors BFU-E (burst-forming unit erythrocyte), CFU-MEG (colony-forming unit megakaryocyte), CFU-Eo (colony-forming unit eosinophil) and CFU-GM (colony-forming unit granulocyte-monocyte). The differentiation of CFU-GEMM is triggered by IL-3 (interleukin-3, also named multi-colony stimulating factor or multi-CSF) and GM-CSF (granulocyte-macrophage colony stimulating factor).
The myeloid precursor BFU-E further differentiates to CFU-E (colony-forming unit erythrocyte) and, finally, to red blood cells. Protein factors required for these differentiation steps are IL-3, GM-CSF and erythropoietin.
CFU-MEG gives rise to the platelet-producing megakaryocytes in the presence of IL-3, GM-CSF and erythropoietin.
CFU-GM develops to monocytes/macrophages in the presence of IL-3, GM-CSF and M-CSF (macrophage colony stimulating factor) whereas in the presence of IL-3, GM-CSF and G-CSF (granulocyte colony stimulating factor) granulocytes are produced.
G-, M-, GM-CSF, and IL-3 (multi-CSF) have originally been detected in the murine system. Meanwhile the corresponding human factors also have been described. The properties of the mouse and human factors are similar (for review see S. C. Clark and R. Kamen, Science 236: 1229-37, 1987).
Diseases caused by a deficiency in the proper regulation of hematopoiesis are known and are of significance. Examples for such diseases are hematopoietic dysfunctions such as dyserythropoiesis, refractory anemia, or dyshematopoiesis. Another problem relating to hematopoiesis is the slow repair in aplasya after bone marrow transplantation. Mainly the occurence of granulocytes in the blood needs at least a few weeks after grafting. Cells of the myeloid lineage can also give rise to tumors. These tumors are leukemias of undifferentiated myeloid cells such as myelomonocytic leukemia or myeloid acute leukemia.
OBJECT OF THE INVENTION
It is an object of the invention to provide means for the regulation of hematopoiesis in individuals with a hematopoietic dysfunction. Another object is to provide means for the treatment of tumours of undifferentiated myeloid cells by differentiating the cells to a non-malignant state.
Surpr
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Debre Patrice
Mossalayi Mohammad D.
Ciba-Geigy Corporation
Fishman Irving M.
Ikeler Barbara J.
Kaiser Karen G.
Koh Choon P.
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