How researchers used CRISPR gene editing to send immune cells after cancer

Last week, researchers published the results of a clinical trial that used CRISPR gene editing to create immune cells that target cancer. The trial was short-lived, and the recombinant immune cells were not particularly effective against the cancer. But the technology, or something similar, could be used in further trials to attack cancer and treat various diseases.

Therefore, the trial provides a good opportunity to go through and explain what was done and why it was done. But if you go back and re-read the first sentence, there was a lot going on here, so there’s a fair amount to explain.

Cancer and the immune system

Cancers and the immune system have a complex relationship. The immune system can eliminate many cancers before they become a problem – people who take immunosuppressive drugs have a higher risk of developing cancer because this function is inhibited. And, even after tumors form, there is often an immune response to the cancer. Cancer cells develop the ability to evade and/or suppress the immune system, allowing them to continue to grow even when the immune system is active.

There are two main ways in which these interactions are targeted by cancer therapies. An approach, which In the year In 2018, they won the Nobel Prize in MedicineIt involves blocking proteins that cause tumors to turn back the immune system. These drugs restore the immune system and help to get rid of some types of cancer.

This same Nobel honored an alternative method of revitalizing the immune response: triggering an influx of tumor-attacking immune cells. The approach, collectively known as CAR-T therapy, involves taking immune cells from the patient, reprogramming them to attack a tumor, growing large numbers of the modified cells in culture, and finally returning them to the patient. The presentation saw some. Success in clinical trialsand there were commercialized versions of CAR-T therapy. FDA approved.

The key to reprogramming T cells to attack cancer involves hijacking the system these immune cells normally use to attack infected or foreign cells. T cells produce a complex of proteins called the T cell receptor (TCR) that recognizes when other cells make abnormal proteins due to pathogens or mutations. The TCR has two parts: a constant part that is the same in all T cells and a part that binds to signaling networks inside the cell. and a variable site that helps identify specific and unusual proteins in different cells.

Thus, when the TCR variable recognizes an abnormal protein, it activates T cell signaling networks.

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