US 7,198,948 B2Granted

Methods and compositions for obtaining mature dendritic cells

AssigneesThe Rockefeller University, Argos Therapeutics, Inc.

InventorsRalph M. Steinman, Nina Bhardwaj, Gerold Schuler

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Abstract

We describe an improved method for generating sizable numbers of mature dendritic cells from nonproliferating progenitors in human blood. The first step or “priming” phase is a culture of T cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4 to produce immature dendritic cells. The second step or “differentiation” phase requires the exposure to dendritic cell maturation factor such as monocyte conditioned medium. Using this two-step approach, substantial yields are obtained. The dendritic cells derive from this method have all the features of mature cells. They include a stellate cell shape, nonadherence to plastic, and very strong T cell stimulatory activity. The mature dendritic cells produced according to this invention are useful for activating T cells.

Claims9

Dependent claims

An in vitro method for producing stable mature dendritic cells from pluripotential cells, comprising:

a) contacting said pluripotential cells having the potential of expressing either macrophage or dendritic cell characteristics with a combination of GM-CSF and IL-4 or IL-13 for a time sufficient to produce immature dendritic cells, and
b) adding a composition selected from the group consisting of peripheral blood mononuclear cell conditioned medium, monocyte conditioned medium and fixed Staphylococcus aureus Cowan 1 strain (SACS) to the immature dendritic cells produced in step (a) and culturing the cells for a time sufficient for the immature dendritic cells to produce stable mature dendritic cells that express a characteristic of mature dendritic cells,
wherein the characteristic is selected from the group consisting of increased CD83 expression, increased CD86 expression, decreased CD115 expression, and decreased CD32 expression relative to the immature dendritic cells.

Dependencies are inferred from the claim text.

Facts

Application: 10/047,072Filed 15 Jan 2002 · continuation
Priority: 12 Feb 1996
Published: US 2002/0160430 A131 Oct 2002
Granted: 3 Apr 2007
Term ends: Not estimatedThe source records don’t support an estimate.

Classification11 codes

C12N 5/0639
Cells from the blood or the immune system: dendritic cells, e.g. Langherhans cells in the epidermis
A61K 40/19
Characterised by the cell type used: dendritic cells
A61K 40/24
Characterised by the effect or the function of the cells: antigen-presenting cells [APC]
A61K 40/4235
Cytokines: interferons [IFN]

Family

Application08/600,483Parent of this continuation · filed 12 Feb 1996
US 2002/0160430 A1Pre-grant publication · published 31 Oct 2002
US 2003/0096314 A1Published application
US 7,659,119 B2Related patent
US 7,198,948 B2This patent

From the US filing history. Foreign family members aren’t listed.