Applying Chimeric Receptor Antigens to Natural Killer Cells to Target Solid Cancers

Chimeric antigen receptor (CAR) technology was first applied to T cells of the adaptive immune system. A patient's T cells are extracted, engineered to express a surface feature that matches to the patient's cancer cells, expanded in culture, and introduced back into the body. This has proven to be highly effective against forms of leukemia. Researchers are attempting to apply this approach to other varieties of immune cell, and thus allow a greater range of efficacy against various classes of cancer. Here, researchers report on their efforts to engineer natural killer cells to recognize patient cancers.

Modified natural killer (NK) cells can differentiate between cancer cells and healthy cells. The experimental treatment is an alternative to chimeric antigen receptor T-cell therapy, or CAR-T. The engineered T-cells used in CAR-T therapy are highly effective against some blood-borne cancers but cannot distinguish between cancerous and non-cancerous cells. So while they offer important benefits, they are not uniformly applicable to all forms of cancer. In patients with solid tumors, the T-cells can cause devastating, even lethal side effects.

The team behind the research wanted a treatment with the same power as CAR-T, but which could be used safely against solid-tumor cancers. They first propagated natural killer cells taken from the blood of patients with breast cancer. Such cells perform a similar function to T-cells in the immune system. The researchers then genetically modified them to target specific receptors on cancer cells, successfully testing the CAR-NK cells in the laboratory on tumor cells derived from breast cancer patients

"The efficacy we see with CAR-NK cells in the laboratory is very promising and seeing that this technology is feasible is very important. Now, we have much better and safer options for solid tumors. These CAR-NK cells are a little bit smarter, in a way, in that they only kill the enemy cells and not good cells that happen to have the same marker. These engineered CAR-NK cells are an important step towards having a viable immunotherapy option in this large group of patients."


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