the “killer cells” programmed against the malignant cells

The ESSENTIAL

• Of the killer cells” NK-reprogrammed allow you to more effectively target the malignant cells of leukemia.

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Affecting an average of 9 000 people in France, the leukemia is a form of blood cancer manifested by the proliferation of young cells in the bone marrow and the blood.

This is the most frequently immature cells that, instead of ripen and to ensure the transport of oxygen, coagulation and the defence of our organism against microbes, remain blocked and invade the bone marrow, which prevents the latter to create normal blood cells and functional.

When occurs in the body a cancer, including leukemia, natural killer cells, so-called “NK cells” as part of the innate immune system, are the first to respond by identifying and targeting the malignant cells. But so far, their effectiveness was limited.

In the creating from induced pluripotent stem cells (iPSC) and deleting their gene ICHS, researchers from the school of medicine of the university of California, San Diego have stepped up their activity and their effectiveness. Their work is published on the website of the magazine Cell Stem Cell.

An improvement in the activation of NK cells

To increase their effectiveness against malignant cells of leukemia, the researchers first created of NK cells from induced pluripotent stem cells (iPSC). Derived from skin cells or blood, they have been reprogrammed back to a pluripotent state of an embryonic type, and then directed to become NK cells. This strategy allows to obtain a cell population, standardised, rather than having to isolate the cells as a function of the patient.

In a second step, the researchers deleted a gene called ICHS in NK cells derived from stem cells. This gene regulates the expression of a protein that suppresses the signaling of cytokines, molecules that, in the event of infection, inflammation, or trauma, can signal to other cells of the immune system.

“We found that NK cells derived from the iPSC, including the ICHS has been deleted, were able to effectively cure mice that contain cells of human leukemia, whereas the mice treated with the NK-cell non-modified died of leukemia,” explains the lead author of the study Dan Kaufman. “These studies demonstrate that we can now change the NK cells derived from the iPSC to eliminate a gene inhibitor to the interior of the cell in order to improve the activation of NK cells.”

According to the researcher, this deactivation of the gene ICHS enhances the function of NK cells by reprogramming metabolically. They are then more efficient in the use of energy, which improves their function in vivo”.

Now, the science team is working on the transposition of these results into a clinical therapy. “As the NK cells derived from iPSC are currently undergoing clinical trials for treating both hematologic malignancies of the blood and solid tumors, we believe that the cells iPSC-NK devoid of ICHS will be able to provide a treatment even more effective,” concludes the Pr Kaufman.

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