Generation and use of dendritic cells

Patent Number: 7,405,076

Plasticity of stem cells to differentiate into various tissues is often a subject of much debate, especially in terms of bone marrow hematopoietic stem cells becoming hepatocytes or cardiac cells.  While some scientists state that a hematopoietic stem cell will only differentiate into blood cells, others point to the clinical evidence that administration of, for example bone marrow cells, into patients with liver or heart failure induces a clinical benefit.  This of course has been demonstrated in animal models of liver regeneration and heart failure.  What is even more controversial is if cells that have already differentiated can then become cells of other lineages.  For example, there are reports of monocytes being able to become islet cells.

One accepted differentiation technique is the generation of dendritic cells from monocytes.  Dendritic cells are a very important cell type since the dendritic cell is the only cell that can activate naive T cells.  So it has become common practice to generate dendritic cells from patients with cancer, insert a cancer gene or protein into the dendritic cell, and use this to stimulate T cell responses against the tumor.  As you can imagine, many types of methods of generating dendritic cells have been developed.  For example, US patent # 7,338,676 covers the use of pine cone extracts for inducing differentiation of dendritic cells.

The current patent teaches the substitution of IL-4, with IL-13 in the generation of dendritic cells from monocytes.  Classically, peripheral blood monocytes are collected from patients, treated with IL-4 and GM-CSF and after approximately a week of culture dendritic cells are obtained.  In the current patent IL-13 is used together with interferon beta.  This allows the generation of IL-3 receptor expressing dendritic cells, which are subsequently induced to mature by exposure to either virus, bacterium, lipopolysaccharide (LPS), nucleic acid, or a combination. 

In the summary of the invention, the inventors state that the IL-3 receptor expressing dendritic cell they are generating is more stable and more potent than previous types of dendritic cells.  This is supported by data in the examples section where it was demonstrated that the dendritic cells generated by the inventors were more potent than GM-CSF + IL-4 generated dendritic cells in terms of stimulating production of interferon gamma from T cells.

This patent would be very useful for companies trying to get into the area of dendritic cell immunotherapy that have freedom to operate issues with the actual dendritic cell generation patents.

View this patent on the USPTO website.