Title - A METHOD FOR PRODUCING ISOLATED, PARTIALLY MATURE, AND ACTIVATED HUMAN DENDRITIC CELLS

Abstract

This description provides cell populations comprising partially mature and optimally activated dendritic cells, which can be used for administration to individuals with cancer and / or a tumor. These partially matured dendritic cells, which have been exposed to a dendritic cell maturation agent for a variable period of approximately 10 to 19 hours, efficiently capture and process tumor antigens in the tumor site, complete maturation, and can subsequently migrate to the lymph nodes of a treated individual. Once in the lymph node, the dendritic cell presenting antigen, now fully mature, secretes the appropriate cytokines (e.g., TNFα, IL-6, IL-8, and / or IL-12) and comes into contact with T cells, inducing a substantial and optimal antitumor clinical and / or immune response.Composition.

Claims

1. A method for producing isolated, partially mature, activated human dendritic cells, excluding the isolated, partially mature, activated human dendritic cells produced by said method, and the cells of the cell population, of dendritic precursor cells used in the method, characterized in that it comprises: i) culturing a cell population comprising an enriched population of human monocytic dendritic cell precursors with a tissue culture medium, supplemented with a dendritic cell differentiation agent consisting of 500 U / mL GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) and between 1 and 10% of a human or animal protein without other cytokines, or 500 U / mL GM-CSF in combination with 500 U / mL of interleukin 4 (IL-4), interleukin 7 (IL-7),interleukin-13 (IL-13) or interleukin 15 (IL-15) to differentiate human monocytic dendritic cell precursors into immature human dendritic cells; ii) culturing the cell population enriched for immature human dendritic cells with a dendritic cell maturation agent comprising between 10 5 and 10 7 colony-forming units (cfu) per milliliter of Bacillus Calmette-Guerin (BCG) tissue culture medium and between 100 and 1000 units of interferon  (IFN) per milliliter of tissue culture medium in order to activate immature human dendritic cells for 16 hours without contact with an antigen; where partially mature dendritic cells demonstrate upregulation in the expression of costimulatory molecules CD80, CD86, and / or CD54, maintain the ability to capture and process antigen, and produce one or more of tumor necrosis factor α (TNFα), interleukin-6 (IL-6),and / or interleukin-8 (IL-8); and iii) isolating and washing activated human dendritic cells. Seven claims follow.