Selective expansion of target cell populations

• US 6,338,942 B2
• Filed: 04/12/1999
• Issued: 01/15/2002
• Est. Priority Date: 05/19/1995
• Status: Expired due to Term

• Current Assignee: ViaCord LLC (Revvity, Inc.)
• Original Assignee: t. Breeders, Inc. (Revvity, Inc.)
• Inventors: Kraus, Morey, Wilder, Paul T., Friberg, Jill
• Primary Examiner(s): Saunders, David
• Assistant Examiner(s): Tung, Mary Beth
• Application Number:
  US09/290,712
• Publication Number:
  US 20010036663A1
• Time in Patent Office: 1,009 Days
• Field of Search: 435/372, 435/2, 435/374, 435/377, 435/395, 435/402, 435/403
• US Class Current: 435/2
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C12N 2500/90 Serum-free medium, which may still contain naturally-sourced components
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors

Abstract

Methods and systems are provided for the selective expansion of target cell populations, and methods of treating patients with cell populations and products.

Claims

1. A method of selective expansion of a target population of cells, said method comprising:

(a) introducing a starting sample of cells, containing cells of the target population or a progenitor to the target population, into a growth medium;

(b) causing cells of the target cell population to divide, the cell division resulting in a relative increase in the number of the target cells; and

(c) concurrently with, intermittently during or following step (b), contacting the cells with a selection element, comprising a plurality of selective binding molecules with specific affinity either for target cells or for a first population of non-target cells, so as to select cells of the target population; and

(d) following selection step (c), causing cells of the target population to divide;

wherein during the division of step (d), there is at least a one day period during which the cell division of step (d) results in a relative increase in tile number of target cells that is at least as great as the relative increase during the division of step (b).

2. The method of claim 1 wherein said selective binding molecules are specific for said target cells.

3. The method of claim 1 wherein said selective binding molecules are specific for non-target cells.

4. The method of claim 2, further comprising, prior to step (a), contacting said starting sample of cells with a selection element comprising selective binding molecules with specific affinity for a second population of non-target cells.

5. The method of claim 1, further comprising, during step (c), removing cells from said growth medium.

6. The method of claim 5, wherein the removed cells are cells of said target cell population.

7. The method of claim 5 wherein the removed cells are non-target cells.

8. The method of claim 1 wherein said starting sample of cells includes said target cells, and said expansion is clonogenic.

9. The method of claim 1 wherein said starting sample of cells includes progenitors of said target cells.

10. The method of claim 1, further comprising removing the growth medium prior to said contacting step.

11. The method of claim 1, wherein said selection element comprises a solid support to which said selective binding molecules are bound.

12. The method of claim 11 wherein said growth medium is disposed in or caused to flow through a chamber.

13. The method of claim 12 further comprising causing said growth medium to recycle through said chamber, flowing from an inlet, through said chamber, to an outlet of said chamber, and returning from the outlet to the inlet via a conduit.

14. The method of claim 2 wherein said selective binding molecules bind to a cell surface antigen on cells of said target cell population but not on cells not in said target cell population.

15. The method of claim 14 wherein said selective binding molecule is a biotinylated antibody specific for an antigen on the surfaces of said cells of said target cell population.

16. The method of claim 3 wherein said selective binding molecules bind to a cell surface antigen that is on cells of the non-target cell population but not on cells of said target cell population.

17. The method of claim 11 further comprising the step of causing plasma to bind to regions of said solid support on which selective binding molecules are not present.

18. The method of claim 17 wherein said plasma is autologous plasma.

19. The method of claim 17 wherein said plasma is a type-matched allogeneic plasma.

20. The method of claim 11, further comprising the step of contacting the solid support with an agent that is capable of binding to regions of said solid support on which said selective binding molecules are not present to prevent non-specific interaction between said regions and materials contacting said solid support.

21. The method of claim 1 wherein said growth medium is conditioned by cells present in the growth medium.

22. The method of claim 21 further comprising causing the growth medium to recycle through a fluid flow loop, thereby enhancing the level of conditioning.

23. The method of claim 22 further comprising concurrently removing dividing cells from the fluid flow loop during recycling.

24. The method of claim 1, further comprising regulating the oxygen saturation of the growth medium to be from 0% to 20% relative to the solubility of oxygen in said fluid at equilibrium with air at 37°

C. and 1 atm pressure.

25. The method of claim 1 wherein the duration of the period is at least 5 days.