Method of enhancing proliferation or differentiation of hematopoietic stem cells using Wnt polypeptides

• US 5,851,984 A
• Filed: 08/16/1996
• Issued: 12/22/1998
• Est. Priority Date: 08/16/1996
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Matthews, William, Austin, Timothy W.
• Primary Examiner(s): Fitzgerald, David L.
• Assistant Examiner(s): Basham, Daryl A.
• Application Number:
  US08/696,566
• Time in Patent Office: 858 Days
• Field of Search: 435/2, 424/85.1, 424/85.2, 514/2
• US Class Current: 514/7.7
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07K 14/475 Growth factors; Growth regulators
• CPC Class Codes: C12N 2799/027 where the vector is derived from a retrovirus

Abstract

Uses for Wnt polypeptides in hematopoiesis are disclosed. In particular, in vitro and in vivo methods for enhancing proliferation or differentiation of a hematopoietic stem/progenitor cell using a Wnt polypeptide, and optionally another cytokine, are described.

Claims

1. A method for enhancing proliferation or differentiation of a hematopoietic stem/progenitor cell comprising exposing the cell to an amount of isolated Wnt polypeptide which is effective for enhancing proliferation or differentiation of the cell.

2. The method of claim 1 wherein the cell is a CD34⁺ cell.

3. The method of claim 1 wherein the cell is a AA4⁺ cell.

4. The method of claim 1 wherein the cell is a flASK cell.

5. The method of claim 1 which enhances proliferation of the cell.

6. The method of claim 1 which enhances differentiation of the cell.

7. The method of claim 1 further comprising exposing the cell to a further cytokine.

8. A The method of claim 7 wherein the further cytokine is a lineage-specific cytokine.

9. The method of claim 7 wherein the further cytokine is selected from the group consisting of thrombopoietin (TPO);

erythropoietin (EPO);

macrophage-colony stimulating factor (M-CSF);

granulocyte-macrophage-CSF (GM-CSF);

granulocyte-CSF (G-CSF);

interleukin-1 (IL-1);

IL-1α

;

IL-2;

IL-3;

IL4;

IL-5;

IL-6;

IL-7;

IL-8;

IL-9;

IL-11;

IL10;

IL-12;

leukemia inhibitory factor (LIF) and kit ligand (KL).

10. The method of claim 1 wherein the cell is in cell culture.

11. The method of claim 1 wherein the cell is present in a mammal.

12. The method of claim 11 wherein the mammal is a human.

13. The method of claim 11 wherein the mammal is suffering from, or is susceptible to, decreased blood cell levels.

14. The method of claim 13 wherein the decreased blood cell levels are caused by chemotherapy, radiation therapy, or bone marrow transplantation therapy.

15. A method for repopulating blood cells in a mammal comprising administering to the mammal a therapeutically effective amount of a Wnt polypeptide.

16. The method of claim 15 wherein the blood cells are erythroid cells.

17. The method of claim 15 wherein the blood cells are myeloid cells.

18. The method of claim 15 wherein the blood cells are lymphoid cells.

19. The method of claim 15 comprising administering a further cytokine to the mammal in an amount which leads to a synergistic repopulation of the blood cells in the mammal.

20. The method of claim 19 wherein the further cytokine is erythropoietin (EPO);

granulocyte-macrophage-colony stimulating factor (GM-CSF);

kit ligand (KL);

or interleukin-3 (IL-3).