Methods and compositions for modulating peripheral immune function

• US 9,655,927 B2
• Filed: 06/06/2014
• Issued: 05/23/2017
• 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): LEAVITT, MARIA GOMEZ
• Application Number:
  US14/298,001
• Publication Number:
  US 20140286918A1
• Time in Patent Office: 1,082 Days
• Field of Search: 435373, 435377, 435455
• 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: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 inhibiting a peripheral inflammatory response in a subject, the method comprising

administering to the subject an effective amount of cells obtained by a method comprising:

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

(b) contacting the cell culture of step (a) with a polynucleotide comprising sequences encoding a Notch intracellular domain (NICD) wherein said polynucleotide does 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;

wherein inhibition of the peripheral inflammatory response is mediated by one or more of;

(i) inhibition of helper T-cell proliferation;

(ii) expansion of a regulatory T-cell population;

(iii) inhibition of differentiation of a monocyte to a dendritic cell;

(iv) inhibition of dendritic cell maturation;

(v) alteration of the cytokine profile of a T-cell or a monocyte from one that is pro-inflammatory to one that is anti-inflammatory; and

(vi) reduced production of interleukin-10 (IL-10) by a T-cell or a monocyte.

2. The method of claim 1, wherein said inhibiting a peripheral inflammatory response comprises inhibition of activation of peripheral T-cells.

3. The method of claim 2, wherein said activation of peripheral T-cells comprises expression of CD69 by the T-cells;

expression of HLA-DR by the T-cells, or expression of both CD69 and HLA-DR by the T-cells.

4. The method of claim 2, wherein said activation of peripheral T-cells comprises proliferation of CD4⁺ T-cells.

5. The method of claim 1, wherein said helper T-cell proliferation, or said production of IL-10 by a T-cell, is associated with the pathology of rheumatoid arthritis.

6. The method of claim 1, wherein said dendritic cell maturation comprises an increase in expression of CD86 by the dendritic cell.

7. The method of claim 1, wherein the peripheral inflammatory response results from an allogeneic transplantation, ischemia or necrosis.

8. The method of claim 1, wherein the peripheral inflammatory response results from graft-versus-host disease (GVHD) or graft rejection.

9. The method of claim 1, wherein the peripheral inflammatory response results from an autoimmune disorder.

10. The method of claim 9, wherein the autoimmune disorder is selected from the group consisting of multiple sclerosis, ulcerative colitis, chronic obstructive pulmonary disease (COPD), asthma, lupus and Type I diabetes.