TREATMENT OF GRAFT-VERSUS-HOST DISEASE

• US 20080292600A1
• Filed: 05/27/2008
• Published: 11/27/2008
• Est. Priority Date: 06/17/2005
• Status: Active Grant

• Current Assignee: Chul Soo Kim, Moon Hee Lee, Sun U.K. Song
• Original Assignee: INHA Industry Partnership Institute
• Inventors: Kim, Chul Soo, SONG, Sun Uk, Lee, Moon Hee
• Granted Patent: US 9,439,929 B2
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 38/2066 IL-10
• CPC Class Codes: A61K 39/461 characterised by the cell type used
• CPC Class Codes: A61K 39/4621 immunosuppressive or immunotolerising
• CPC Class Codes: A61K 39/46434 Antigens related to induction of tolerance to non-self
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C12N 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)

Abstract

This present application describes a therapeutic agent for treating acute or chronic graft-versus-host disease using clonal marrow stem cells (cMSCs) as active ingredient.

Claims

1. A method of inhibiting activity of T-cell from donor marrow in a subject identified as suffering from graft-versus-host disease, comprising administering to the subject in need thereof a therapeutically effective amount of a population of homogeneous clonal marrow stem cells.

2. The method according to claim 1, wherein a dosage of the stem cells per each administration is between 1×

10⁴ cells/kg body weight to 1×

10⁸ cells/kg weight.

3. The method according to claim 1, wherein the stem cells are isolated using a subfractionation culturing method.

4. The method according to claim 1, wherein the stem cells express CD29, CD44, and CD105 cell surface antigens, but not HLA-DR cell surface antigen.

5. The method according to claim 1, wherein the stem cells express CD29, CD44, CD73 CD90, CD105, and CD166 cell surface antigens but not CD106, CD119, or HLA-DR cell surface antigens.

6. The method according to claim 1, wherein the homogeneous clonal marrow stem cells secretes interleukin-10 at a concentration of at least about 5 ng/ml.

7. A method of treating symptoms of graft-versus-host disease in a subject identified as suffering from graft-versus-host disease, comprising administering to the subject in need thereof a therapeutically effective amount of a population of homogeneous clonal marrow stem cells.

8. The method according to claim 7, wherein the symptom of graft-versus-host disease is in the gastrointestinal tract, sclerotic skin, limitation of oral intake, dryness of eyes, liver symptoms, shortness of breath, or tightness of arms or legs.

9. The method according to claim 8, wherein the gastrointestinal symptom is raised daily volume of stool.

10. The method according to claim 8, wherein the gastrointestinal symptom is inflamed colon.

11. The method according to claim 8, wherein the liver symptom is raised alkaline phosphatase level in blood serum.

12. A method of inhibiting activity of T-cell from donor marrow in a subject identified as suffering from graft-versus-host disease, comprising:

(A) manipulating a biological sample of bone marrow cells, comprising;

(i) allowing the sample of cells to settle in a container;

(ii) transferring supernatant from the container to another container; and

(iii) isolating cells from the supernatant, which has comparatively lower density in the sample to obtain a population of homogeneous clonal marrow stem cells; and

(B) administering to the subject in need thereof a therapeutically effective amount of the population of homogeneous clonal marrow stem cells obtained in (A).

13. The method according to claim 12, wherein the container is treated with a coating.

14. The method according to claim 13, wherein the coating is collagen, poly-lysine, fibrinogen, or gelatin.

15. A method of treating symptoms of graft-versus-host disease in a subject identified as suffering from graft-versus-host disease, comprising:

(A) manipulating a biological sample of bone marrow cells, comprising;

(i) allowing the sample of cells to settle in a container;

(ii) transferring supernatant from the container to another container; and

(iii) isolating cells from the supernatant, which has comparatively lower density in the sample to obtain a population of homogeneous clonal marrow stem cells; and

(B) administering to the subject in need thereof a therapeutically effective amount of the population of homogeneous clonal marrow stem cells obtained in (A).

16. The method according to claim 15, wherein a dosage of the cells is between 1×

10⁴ cell/kg to 1×

10⁸ cell/kg.

17. The method according to claim 15, wherein the cells express CD29, CD44, and CD105 cell surface antigens, but not HLA-DR cell surface antigens.

18. The method according to claim 15, wherein the cells express CD29, CD44, CD73 CD90, CD105, and CD166 cell surface antigens but not CD106, CD119, or HLA-DR cell surface antigens.

19. The method according to claim 15, wherein the population of cells secrete interleukin-10 at a concentration of at least about 5 ng/ml.