Tumor suppression using placental stem cells

• US 20080152624A1
• Filed: 08/03/2007
• Published: 06/26/2008
• Est. Priority Date: 08/04/2006
• Status: Active Grant

• Current Assignee: Celularity, Inc.
• Original Assignee: Anthrogenesis Corporation (Bristol-Myers Squibb Company)
• Inventors: Hariri, Robert J., Ye, Qian, Murray, RoseAnn, Paludan, Casper, Harbacheuski, Ryhor, Edinger, James W.
• Granted Patent: US 7,993,918 B2
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/48 Reproductive organs
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C12N 2501/23 Interleukins [IL]
• CPC Class Codes: C12N 2501/24 Interferons [IFN]
• CPC Class Codes: C12N 2502/025 extra-embryonic cells, e.g. amniotic epithelium, placental cells, Wharton's jelly
• CPC Class Codes: C12N 2502/1388 Mesenchymal stem cells from other natural sources
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 5/0605 Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
• CPC Class Codes: C12N 5/0668 Mesenchymal stem cells from other natural sources
• CPC Class Codes: C12N 5/0693 Tumour cells; Cancer cells
• CPC Class Codes: C12N 5/0694 Cells of blood, e.g. leukemia cells, myeloma cells

Abstract

The present invention provides methods of suppression of tumor cell proliferation and tumor growth using placental stem cells and placental stem cell populations. The invention also provides methods of producing and selecting placental cells and cell populations on the basis of tumor suppression, and compositions comprising such cells and cell populations.

Claims

1. A method of suppressing the proliferation of a plurality of tumor cells comprising contacting said plurality of tumor cells with a plurality of placental stem cells for a time sufficient for said placental stem cells to detectably suppress proliferation of said plurality of tumor cells, as compared to a plurality of said tumor cells not contacted with placental stem cells.

2. The method of claim 1, wherein said placental stem cells:

express CD200 and HLA-G,

express CD73, CD105, and CD200,

express CD200 and OCT-4,

express CD73, CD105, and HLA-G,

express CD73 and CD105, and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the stem cell, when said population is cultured under conditions that allow formation of embryoid-like bodies, and/or

express OCT-4 and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the stem cell, when said population is cultured under conditions that allow formation of embryoid-like bodies.

3. The method of claim 1, wherein said tumor cells are part of a solid tumor.

4. The method of claim 1, wherein said plurality of tumor cells are histiocytic lymphoma cells, chronic myelogenous leukemia cells, acute T-cell leukemia cells, acute myelogenous leukemia cells, colon adenocarcinoma cells, retinoblastoma cells or lung carcinoma cells.

5. The method of claim 1, wherein said contacting is performed in vitro.

6. The method of claim 1, wherein said contacting is performed in vivo.

7. The method of claim 6, wherein said contacting is performed in an individual who comprises said tumor cells.

8. The method of claim 7, wherein said individual is a mammal.

9. The method of claim 8, wherein said mammal is a human.

10. The method of claim 7, wherein said contacting comprises administering said placental cells to said individual intravenously.

11. The method of claim 7, wherein said contacting comprises administering said placental cells to said individual at or adjacent to the site of a tumor.

12. The method of claim 1, wherein at least a portion of said placental stem cells have been engineered to express a cytokine.

13. The method of claims 12, wherein said cytokine is IFN-β

or IL-2.

14. The method of claim 1, additionally comprising contacting said tumor cells with one or more anticancer compounds.

15. The method of claim 1, comprising contacting said tumor cells with a plurality of mesenchymal stem cells.

16. The method of claim 15, wherein said mesenchymal stem cells are bone marrow-derived mesenchymal stem cells.

17. The method of claim 7, comprising administering at least 1×

10⁷ placental stem cells to said individual.

18. The method of claim 7, comprising administering at least 1×

10⁸ placental stem cells to said individual.

19. The method of claim 1, wherein said placental stem cells have been proliferated in vitro for no more than 30 population doublings.

20. The method of claim 1, wherein said placental stem cells have been proliferated in vitro for no more than 10 population doublings.

21. The method of claim 1, wherein said placental stem cells have been cryopreserved and thawed prior to said contacting.

22. The method of claim 1, wherein said placental stem cells suppress said tumor cell proliferation by at least 50% compared to proliferation of an equivalent number of tumor cells in the absence of said placental stem cells.

23. The method of claim 1, wherein said placental stem cells suppress said tumor cell proliferation by at least 75% compared to proliferation of an equivalent number of tumor cells in the absence of said placental stem cells.

24. The method of claim 7, comprising determining that said placental stem cells detectably suppress the proliferation of tumor cells prior to said contacting.

25. The method of claim 24, wherein said sample tumor cells are tumor cells of the same tissue origin as said tumor cells contacted with said placental stem cells.

26. The method of claim 25, wherein said sample tumor cells are tumor cells of an individual.

27. The method of claim 24, wherein said determining comprises determining that said sample tumor cells are detectably suppressed by direct contact with said placental stem cells.

28. The method of claim 24, wherein said determining comprises determining that said sample tumor cells are detectably suppressed by said placental stem cells without direct contact between said placental stem cells and said sample tumor cells.

29. A method of producing a population of placental stem cells, comprising selecting placental stem cells that

(a) adhere to a substrate, and

(b) express CD200 and HLA-G, or

express CD73, CD105, and CD200, or

express CD200 and OCT-4, or

express CD73, CD105, and HLA-G, or

express CD73 and CD105, and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the stem cell, when said population is cultured under conditions that allow formation of embryoid-like bodies, or

express OCT-4, and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the stem cell, when said population is cultured under conditions that allow formation of embryoid-like bodies;

and

determining that said placental stem cells detectably suppress tumor cell proliferation, wherein said tumor cells are histiocytic lymphoma cells, chronic myelogenous leukemia cells, acute T-cell leukemia cells, acute myelogenous leukemia cells, colon adenocarcinoma cells, retinoblastoma cells or lung carcinoma cells; and

and isolating said placental stem cells from other cells to form a cell population.

30. An isolated cell population comprising placental stem cells, wherein said placental stem cells:

(a) adhere to a substrate,

(b) express CD200 and HLA-G, or

express CD73, CD105, and CD200, or

express CD200 and OCT-4, or

express CD73, CD105, and HLA-G, or

express CD73 and CD105, and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the placental stem cells, when said population is cultured under conditions that allow formation of embryoid-like bodies, or

express OCT-4 and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the placental stem cells, when said population is cultured under conditions that allow formation of embryoid-like bodies; and

(c) have been determined to detectably suppress proliferation of said plurality of tumor cells, as compared to a plurality of tumor cells not contacted with placental stem cells.

31. A pharmaceutical composition comprising culture medium conditioned by a plurality of placental stem cells, wherein said placental stem cells

(a) adhere to a substrate,

(b) express CD200 and HLA-G, or

express CD73, CD105, and CD200, or

express CD200 and OCT-4, or

express CD73, CD105, and HLA-G, or

express CD73 and CD105, and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the stem cell, when said population is cultured under conditions that allow formation of embryoid-like bodies, or

express OCT-4, and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the stem cell, when said population is cultured under conditions that allow formation of embryoid-like bodies;

and

(c) have been identified as detectably suppressing proliferation of a tumor cell or population of tumor cells, or growth of a tumor.