Method for enhancing proliferation or differentiation of a cell using OB protein

Abstract

Uses for WSX ligands in hematopoiesis are disclosed. In particular, in vitro and in vivo methods for stimulating hematopoiesis (e.g., myelopoiesis, erythropoiesis and especially, lymphopoiesis) using a WSX ligand (e.g., anti-WSX receptor agonist antibodies or OB protein), and optionally another cytokine, are described.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This is a continuation of U.S. patent application Ser. No. 08 / 667,197 filed Jun. 20, 1996, which claims priority to U.S. Provisional Patent Application No. 60 / 064,855, filed Jan. 8, 1996, hereby incorporated by reference in their entireties.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] The present invention pertains generally to the WSX receptor. In particular, the invention relates to WSX ligands and uses therefor. [0004] 2. Description of the Related Art [0005] Hematopoiesis [0006] The process of blood cell formation whereby red and white blood cells are replaced through the division of cells located in the bone marrow is called hematopoiesis. For a review of hematopoiesis see Dexter and Spooncer (Ann. Rev. Cell Biol. 3:423-441 (1987)). [0007] There are many different types of blood cells which belong to distinct cell lineages. Along each lineage, there are cells at different stages of maturation. Mature blood ce...

AI Technical Summary

Benefits of technology

[0027] In another embodiment, an effective amount of the WSX ligand may be used to improve engraftment in bone marrow transplantation or to stimulate mobilization of hematopoietic stem cells in a mammal prior to harvesting hematopoietic progenitors from the peripheral blood thereof.

[0030] Pharmaceutical compositions of the WSX receptor ECD may further include a WSX ligand. Such dual compositions may be beneficial where it is therapeutically useful to prolong the half-life of WSX ligand and / or activate endogenous WSX receptor directly as a heterotrimeric complex.

[0037] For certain applications, it is desirable to have an agonist antibody which can be screened for as described herein. Such agonist antibodies are useful for activating the WSX receptor for in vitro uses whereby enhancement of proliferation and / or differentiation of a cell comprising the receptor is desired. Furthermore, these antibodies may be used to treat conditions in which an effective amount of WSX receptor activation leads to a therapeutic benefit in the mammal treated therewith. For example, the agonist antibody can be used to enhance survival, proliferation and / or differentiation of a cell comprising the WSX receptor. In particular, agonist antibodies and other WSX ligands may be used to stimulate proliferation of stem cells / progenitor cells either in vitro or in vivo. Other potential therapeutic applications include the use of agonist antibodies to treat metabolic disorders (such as obesity and diabetes) and to promote kidney, liver or lung growth and / or repair (e.g., in renal failure).

[0040] In addition to the above, the invention provides isolated nucleic acid molecules, expression vectors and host cells encoding the WSX receptor which can be used in the recombinant production of WSX receptor as described herein. The isolated nucleic acid molecules and vectors are also useful for gene therapy applications to treat patients with WSX receptor defects and / or to increase responsiveness of cells to WSX ligand.

Problems solved by technology

As stem cells progressively lose their ability to self-renew, they become increasingly lineage restricted.

Due to their low abundance and their existence in both high-affinity and low-affinity forms, biochemical characterization of these receptors has been hampered.

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