BISPECIFIC ANTIBODIES AND AGENTS TO ENHANCE STEM CELL HOMING

• US 20080057053A1
• Filed: 08/31/2006
• Published: 03/06/2008
• Est. Priority Date: 08/31/2006
• Status: Active Grant

• Current Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Original Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Inventors: Stolen, Craig
• Granted Patent: US 8,372,399 B2
• Time in Patent Office: Days
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 2317/31 multispecific

Abstract

A composition having a bispecific antibody which binds a stem cell specific antigen and a tissue, differentiated cell or condition associated antigen and an agent that enhances expression of the tissue, differentiated cell or condition associated antigen, is provided. Also provided are methods of using the bispecific antibodies and/or agents to enhance cell therapy.

Claims

1. A composition, comprising:

a bispecific antibody which binds a stem cell specific antigen and a tissue, differentiated cell or condition associated antigen; and

an agent that enhances expression of the tissue, differentiated cell or condition associated antigen.

2. The composition antibody of claim 1 wherein the tissue is cardiac tissue.

3. The composition antibody of claim 1 wherein the condition is inflammation.

4. The composition antibody of claim 1 wherein the condition is scarring.

5. The composition antibody of claim 1 wherein the condition is heart disease.

6. The composition antibody of claim 1 wherein the condition is diabetes.

7. The composition antibody of claim 1 wherein the condition is Alzheimer'"'"'s disease.

8. The composition antibody of claim 1 wherein the condition is spinal cord damage.

9. The composition antibody of claim 1 wherein the condition is arthritis.

10. The composition of claim 1 wherein the stem cell antigen is CD34, CD133, ABCG2, Sca-1, Stro-1, nestin, PSA-NCAm, P75 neurotrophin, c-kit or CD30.

11. The composition antibody of claim 1 wherein the tissue differentiated cell or condition associated antigen is VAP-1, P-selectin, E-selectin, ICAM, VCAM or VLA.

12. The composition of claim 1 wherein the bispecific antibody binds collagen.

13. The composition of claim 1 further comprising stem cells having the stem cell specific antigen.

14. The composition of claim 13 wherein the stem cells are genetically altered stem cells.

15. The composition of claim 1 wherein the agent is a cytokine, a growth factor or a vector encoding a gene product.

16. The composition of claim 1 wherein the tissue expresses an ectopic antigen.

17. A method of enhancing localization and retention of stem cells, comprising:

delivering to a mammal in need of cell therapy an effective amount of bispecific antibodies which bind a stem cell specific antigen and a tissue, differentiated cell or condition associated antigen, an agent or treatment that enhances expression of the tissue, differentiated cell or condition associated antigen, and donor stem cells.

18. The method of claim 17 wherein the bispecific antibodies are contacted with the donor stem cells prior to delivery.

19. The method of claim 17 wherein the donor stem cells are systemically delivered.

20. The method of claim 17 wherein the donor stem cells are locally delivered.

21. The method of claim 17 wherein the donor stem cells are delivered contemporaneously with the bispecific antibodies.

22. The method of claim 17 wherein the bispecific antibodies are systemically delivered.

23. The method of claim 17 wherein the bispecific antibodies are delivered via a catheter.

24. The method of claim 17 wherein the agent is locally delivered prior to the administration of the bispecific antibodies or the cells.

25. The method of claim 17 wherein the donor stem cells are bone marrow cells (BMCs) or mesenchymal stem cells (MSCs).

26. The method of claim 17 wherein the stem cells are autologous or allogenic stem cells.

28. The method of claim 17 or 27 wherein the mammal is a human.

29. The method of claim 17 or 27 wherein the treatment is inducing hypoxia, pacing with or without synchrony, or heat.

27. A method for targeting stem cells to a site of injury or inflammation, comprising:

delivering to a mammal an effective amount of bispecific antibodies which bind a stem cell specific antigen and an antigen associated with injury or inflammation, an agent or treatment that enhances expression of the injury or inflammation associated antigen, and donor stem cells having the stem cell specific antigen, wherein the agent is locally delivered.

30. A method for targeting stem cells to a selected location in a mammal, comprising delivering to a mammal in need of cell therapy an effective amount of bispecific antibodies which bind a stem cell specific antigen and a tissue or differentiated cell specific antigen, and donor stem cells, wherein the tissue or differentiated cell specific antigen is specific for neuronal cells, microglial cells, pancreatic cells, cartilage, or endothelial cells.

31. The method of claim 30 wherein the mammal has Alzheimer'"'"'s disease.

32. The method of claim 30 wherein the mammal has spinal cord damage.

33. The method of claim 30 wherein the mammal has diabetes.

34. The method of claim 30 wherein the mammal has restenosis.

35. The method of claim 30 wherein the mammal has arthritis.

36. A composition comprising a bispecific antibody which binds a stem cell specific antigen and a tissue, differentiated cell or condition associated antigen, which antibody is linked to a protein or drug that enhances cell engraftment, enhances cell extravasation, enhances angiogenesis, or inhibits apoptosis.

37. The composition of claim 36 wherein the protein or drug is a vasodilator, a matrix degrading enzyme or a component of a bacterial cell.

38. The composition of claim 36 wherein the protein or drug is substance P, matrix metalloproteinase, elastase, heparanase, IL-1, TNF-α

, IFN-γ

, LPS, or a growth factor.

39. The composition of claim 38 wherein the growth factor is VEGF, IGF or FGF.