Activation and expansion of cells

• US 20040241162A1
• Filed: 01/20/2004
• Published: 12/02/2004
• Est. Priority Date: 02/24/2000
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Xcyte Therapies, Inc. (Cyclacel Pharmaceuticals Incorporated)
• Inventors: Berenson, Ronald J., Bonyhadi, Mark, Kalamasz, Dale, Craig, Stewart, Hardwick, Alan, Saund, Narinder, Law, Che, McMillen, David, Chana, Harjinder Singh
• Granted Patent: US 7,541,184 B2
• Time in Patent Office: Days
• US Class Current: 424/144.1
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 2239/48 Blood cells, e.g. leukemia or lymphoma
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2806 against CD2
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/2812 against CD4
• CPC Class Codes: C07K 16/2815 against CD8
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 16/2821 against ICAM molecules, e.g. CD50, CD54, CD102
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 16/2833 against MHC-molecules, e.g. HLA-molecules
• CPC Class Codes: C07K 16/2845 against integrin beta2-subunit-containing molecules, e.g. CD11, CD18
• CPC Class Codes: C07K 16/2854 against selectins, e.g. CD62
• CPC Class Codes: C07K 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 16/2875 : against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 against NGF C07K16/22, against TNF C07K16/241
• CPC Class Codes: C07K 16/2878 : against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 16/289 : against CD45
• CPC Class Codes: C07K 16/2896 : against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C12N 2500/32 : Amino acids
• CPC Class Codes: C12N 2501/23 : Interleukins [IL]
• CPC Class Codes: C12N 2501/51 : B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand)
• CPC Class Codes: C12N 2501/515 : CD3, T-cell receptor complex
• CPC Class Codes: C12N 2501/53 : CD2
• CPC Class Codes: C12N 2501/59 : Lectins
• CPC Class Codes: C12N 2533/12 : Glass
• CPC Class Codes: C12N 2533/14 : Ceramic
• CPC Class Codes: C12N 2533/18 : Calcium salts, e.g. apatite, Mineral components from bones, teeth, shells
• CPC Class Codes: C12N 2533/30 : Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 2533/40 : Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 2533/54 : Collagen; Gelatin
• CPC Class Codes: C12N 2533/70 : Polysaccharides
• CPC Class Codes: C12N 2533/72 : Chitin, chitosan
• CPC Class Codes: C12N 2533/90 : Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
• CPC Class Codes: C12N 5/0635 : B lymphocytes
• CPC Class Codes: C12N 5/0636 : T lymphocytes
• CPC Class Codes: C12N 5/0647 : Haematopoietic stem cells; Uncommitted or multipotent progenitors

Abstract

The present invention relates generally to methods for activating and expanding cells, and more particularly, to a novel method to activate and/or stimulate cells that maximizes the expansion of such cells to achieve dramatically high densities. In the various embodiments, cells are activated and expanded to very high densities in a short period of time. In certain embodiments, cells are activated and expanded to very high numbers of cells in a short period of time. Compositions of cells activated and expanded by the methods herein are further provided.

Claims

1-18. -18. (Canceled).

22. A method for activating and expanding a population of regulatory T cells by cell surface moiety ligation, comprising:

a. providing a population of cells wherein at least a portion thereof comprises regulatory T cells;

b. contacting said population of cells with a surface, wherein said surface has attached thereto a first agent that ligates a first T cell surface moiety of a regulatory T cell, and the same or a second surface has attached thereto a second agent that ligates a second moiety of said regulatory T cell, wherein said ligation by the first and second agent induces proliferation of said regulatory T cell.

23. The method according to claim 22 wherein the first agent is an anti-CD3 antibody and the second agent is an anti-CD28 antibody.

25. A composition comprising a population of T cells according to claim 22 wherein said population of cells wherein at least a portion thereof comprises T cells is collected from a healthy individual for use at a later time point for the treatment of cancer in said individual.

26. The composition of claim 25 wherein said cancer is selected from the group consisting of melanoma, non-Hodgkin'"'"'s lymphoma, cutaneous T cell lymphoma, Hodgkin'"'"'s disease, leukemia, plasmocytoma, sarcoma, glioma, thymoma, breast cancer, prostate cancer, colo-rectal cancer, kidney cancer, renal cell carcinoma, uterine cancer, pancreatic cancer, esophageal cancer, brain cancer, lung cancer, ovarian cancer, cervical cancer, testicular cancer, gastric cancer, esophageal cancer, multiple myeloma, hepatoma, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), and chronic lymphocytic leukemia (CLL).

27. The method according to claim 26 wherein said cancer comprises multiple myeloma.

28. The method according to claim 26 wherein said cancer comprises CLL.

24. (Canceled)

29. A method for treating a cancer comprising:

a. contacting a population of cells obtained from a patient, wherein at least a portion of said population comprises T cells, with a surface, wherein said surface has attached thereto a first agent that ligates a first cell surface moiety of a T cell, and the same surface has attached thereto a second agent that ligates a second moiety of said T cell, wherein said ligation by the first and second agent induces proliferation of said T cell, and wherein said surface is present at a ratio of said surface to said cells such that at least one population of antigen-specific T cells is expanded at least about 10 fold in about 8 days;

b. administering to said patient the population of T cells from (a); and

thereby treating the cancer.

19. The method according to claim 29 wherein said cancer is selected from the group consisting of melanoma, non-Hodgkin'"'"'s lymphoma, cutaneous T cell lymphoma, Hodgkin'"'"'s disease, leukemia, plasmocytoma, sarcoma, glioma, thymoma, breast cancer, prostate cancer, colo-rectal cancer, kidney cancer, renal cell carcinoma, uterine cancer, pancreatic cancer, esophageal cancer, brain cancer, lung cancer, ovarian cancer, cervical cancer, testicular cancer, gastric cancer, esophageal cancer, multiple myeloma, hepatoma, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), and chronic lymphocytic leukemia (CLL).

20. The method according to claim 29 wherein said cancer comprises multiple myeloma.

21. The method according to claim 29 wherein said cancer comprises CLL.