# US 2010/0167332 A1 · Induction of dendritic cell development with macrophage-colony stimulating factor (m-csf)

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- Number: US 2010/0167332 A1
- Document ID: US20100167332A1
- Status: Published application
- Kind: A1
- Application number: 12/596,175
- Filed: 2008-04-25
- Published: 2010-07-01
- Earliest claimed: 2007-04-27
- Assignees: Bavarian Nordic A/S
- Inventors: Hubertus Hochrein; Meredith O'Keeffe
- Web page: https://patentgrep.com/patent/US20100167332A1

## CPC

- C12N 5/0639: {Dendritic cells, e.g. Langherhans cells in the epidermis}
- A61K 40/19: Dendritic cells
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/428: {Undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor}
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- A61K 2039/55522: {Cytokines; Lymphokines; Interferons}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- C12N 2500/70: Undefined extracts
- C12N 2500/72: from bacteria
- C12N 2500/74: from fungi, e.g. yeasts
- C12N 2500/76: from plants
- C12N 2501/056: Immunostimulating oligonucleotides, e.g. CpG
- C12N 2501/22: Colony stimulating factors (G-CSF, GM-CSF)
- C12N 2501/24: Interferons [IFN]
- C12N 2501/25: Tumour necrosing factors [TNF]
- C12N 2710/24143: viral genome or elements thereof as genetic vector
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

A method of inducing dendritic cell (DC) development by administering Macrophage-Colony Stimulating Factor (M-CSF) is provided. M-CSF induces DCs to differentiate into Subtypes, for example plasmacytoid DCs and conventional DCs. Said differentiation is independent of Fms-like-Tyrosine- Kinase 3-Ligand (FL) and/or Granulocyte-Macrophage-Colony Stimulating Factor (GM-CSF). Induction with M-CSF can be achieved in vitro from hematopoietic precursors, such as bone marrow cells, or in vivo. In vitro, M-CSF-derived DCs can be used to produce cytokines and to stimulate other immune response cells. M-CSF can also be used to induce precursor cells removed from an animal to develop into DCs. In addition, these isolated DCs can be exposed to antigens to stimulate a specific immune response when reintroduced into the animal. Treatments for Cancers, such as Acute Myeloid Leukemia, and autoimmune diseases such as Systemic Lupus Erythematosus, are also provided in the invention.

## Claims

### Claim at position 1

1-66. (canceled)

### Claim 67

A method of Fms-like-Tyrosine-Kinase 3-Ligand- (FL)- and Granulocyte-Macrophage-Colony Stimulating Factor- (GM-CSF)-independent generation of dendritic cells (DCs) comprising:
(a) culturing hematopoietic precursor cells;
(b) administering Macrophage-Colony Stimulating Factor (M-CSF) to the precursor cells; and
(c) quantitating the number of plasmacytoid dendritic cells (pDCs);
wherein the administration of M-CSF causes an FL-independent and GM-CSF-independent generation of pDCs from the hematopoietic precursor cells.

### Claim 68 (depends on 67)

The method of claim 67, further comprising quantitating the number of conventional dendritic cells (cDCs).

### Claim 69 (depends on 67)

The method of claim 67, wherein the precursor cells are bone marrow cells.

### Claim 70 (depends on 67)

The method of claim 67, wherein the numbers of pDCs are quantitated before and after administration of M-CSF and wherein the number of pDCs after M-CSF administration is increased over the number of pDCs before administration of M-CSF.

### Claim 71 (depends on 68)

The method of claim 68, wherein the numbers of cDCs are quantitated before and after administration of M-CSF and wherein the number of cDCs after M-CSF administration is increased over the number of cDCs before administration of M-CSF.

### Claim 72 (depends on 70)

The method of claim 70, wherein the number of pDCs is quantitated by measuring the level of at least one cell surface marker selected from CD11c, CD45R, CD45RA, PDCA-1, CCR9, Ly49Q, Ly6C, Siglec-H, HLA-DR, CD4, CD123, BDCA-2, or BDCA-4.

### Claim 73 (depends on 71)

The method of claim 71, wherein the number of cDCs is quantitated by measuring the level of at least one cell surface marker selected from CD11c, CD11b, CD4, CD8, Sirp-alpha, DEC-205, MHCII, 33D1, HLA-DR, BDCA-1, BDCA-3, or CLEC9A.

### Claim 74 (depends on 67)

The method of claim 67, wherein the DCs are harvested.

### Claim 75 (depends on 67)

The method of claim 67, wherein cytokines produced by the generated DCs are collected.

### Claim 76 (depends on 75)

The method of claim 75, wherein the cytokine produced is selected from the group comprising IFN-α, IFN-R, IL-1, IL-6, IL-8, IL-10, IL-12, IL-15, IL-16, IL-18, IL-23, IL-27, IL-28, IL-29, TNF-α, TNF-(3 and chemokines.

### Claim 77 (depends on 76)

The method of claim 76, wherein the cytokine produced is IFN-α.

### Claim 78 (depends on 67)

The method of claim 67, further comprising exposing the DCs to an antigen.

### Claim 79 (depends on 78)

The method of claim 78, wherein the antigen is derived from a tumor, a virus, bacteria, fungi, parasite, prion, plant, mollusc, arthropod, or from vertebrate toxins.

### Claim 80 (depends on 67)

The method of claim 67, further comprising stimulating the DCs by exposing them to at least one stimulatory agent.

### Claim 81 (depends on 80)

The method of claim 80, wherein the at least one stimulatory agent is IFN-α, IFN-R, IL-6, IL-10, IL-12, TNF-α, a TLR-agonist, virus, bacteria, fungi, plant or parts thereof.

### Claim 82 (depends on 67)

The method of claim 67, wherein the M-CSF is administered in a virus vector.

### Claim 83 (depends on 82)

The method according to claim 82, wherein the virus vector is a poxvirus vector.

### Claim 84 (depends on 83)

The method of claim 83, wherein the poxvirus vector is a Vaccinia virus vector.

### Claim 85 (depends on 84)

The method of claim 84, wherein the Vaccinia virus vector is a Modified Vaccinia virus Ankara (MVA) vector.

### Claim 86 (depends on 67)

The method of claim 67, wherein the M-CSF is administered as a polypeptide or as a nucleic acid that is expressed in the cell.

### Claim 87 (depends on 86)

The method of claim 86, wherein the nucleic acid is DNA or RNA.