Methods and compositions for modulating peripheral immune function

• US RE46,382 E1
• Filed: 10/02/2015
• Issued: 05/02/2017
• Est. Priority Date: 04/06/2011
• Status: Active Grant

• Current Assignee: Sanbio, Inc. (SanBio Co., Ltd.)
• Original Assignee: Sanbio, Inc. (SanBio Co., Ltd.)
• Inventors: Dao, Mo, Case, Casey C.
• Primary Examiner(s): Ponnaluri, Shri
• Application Number:
  US14/874,249
• Time in Patent Office: 578 Days
• Field of Search: 435373, 435377, 435455, 436455
• 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: C12N 15/85 for animal cells
• CPC Class Codes: C12N 2501/2302 Interleukin-2 (IL-2)
• CPC Class Codes: C12N 2501/42 Notch; Delta; Jagged; Serrate
• CPC Class Codes: C12N 2502/1358 Bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: C12N 5/0637 Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg
• CPC Class Codes: C12N 5/0639 Dendritic cells, e.g. Langherhans cells in the epidermis
• CPC Class Codes: C12N 5/0645 Macrophages, e.g. Kuepfer cells in the liver; Monocytes
• CPC Class Codes: C12N 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)

Abstract

Disclosed herein are cell preparations useful for modulating various peripheral immune functions, methods for making said cell preparations, and methods for their use.

Claims

1. A method for modulating production of one or more cytokines by a T-lymphocyte (T-cell) or a monocyte;

the method comprising;

contacting the T-cell or monocyte with an effective amount of SB623 MASC-derived immune modulatory cells;

wherein said contacting results in stimulation of the production of one or more anti-inflammatory cytokines and/or inhibition of production of one or more pro-inflammatory cytokines by the T-cell or the monocyte;

further wherein said SB623 MASC-derived immune modulatory cells are obtained by

(a) providing a culture of marrow adherent stromal cells (MASCs);

(b) contacting the cell culture of step (a) with a polynucleotide comprising sequences encoding the Notch intracellular domain (NICD) wherein said polynucleotide dos not encode a full-length Notch protein;

(c) selecting cells that comprise the polynucleotide of step (b); and

(d) further culturing the selected cells of step (c) in the absence of selection for the polynucleotide, such that said marrow adherent stromal cells are induced to form SB623 MASC-derived immune modulatory cells by expression of the NICD.

2. The method of claim 1, wherein the pro-inflammatory cytokine is interferon gamma (IFN-γ

).

3. The method of claim 1, wherein the pro-inflammatory cytokine is tumor necrosis factor alpha (TNF-α

).

4. The method of claim 1, wherein the anti-inflammatory cytokine is interleukin-10 (IL-10).

5. The method of claim 1, wherein the T cell is a helper T-cell.

6. The method of claim 5, wherein the helper T-cell is T_H1 cell.

7. The method of claim 1, wherein the T-cell is a regulatory T-cell.

8. The method of claim 7, wherein the regulatory T-cell is a T_R1 cell.

9. The method of claim 1, wherein said modulation of cytokine production results in conversion of a T-cell population from one that is pro-inflammatory to one that is anti-inflammatory.