Experimental CRISPR technology shows promise against advanced leukemia

To Michael Le Paige

Teenagers with progressive leukemia currently have no detectable cancer Cells after becoming the first to receive a new kind of treatment Crisper It’s called base editing. However, it is not clear for several years whether she will remain free from this condition.

A 13-year-old girl called Alyssa did not respond to other treatments. As part of her trial, she received immune cells from a donor that were engineered to attack cancer. A test 28 days later revealed she was in remission.

“While these are still preliminary results and will need to be monitored and confirmed over the coming months, they are very noteworthy. Robert ChiesaHe is one of the doctors treating Alyssa, according to a statement released by London’s Great Ormond Street Hospital.

What causes leukemia immunity Cells in the bone marrow grow out of control.Usually after chemotherapy kills all bone marrow cells, the bone marrow is transplantThis works most of the time. If unsuccessful, doctors can try an approach known as CAR-T therapy.

This involves adding genes to a type of immune cell known as T cells to seek out and destroy cancer cells.The modified cells are known as CAR-T cells.

Initially, all CAR-T treatments involved removing an individual’s own T cells and modifying them to replace them. Using another person’s T cells will attack every cell in the recipient’s body. This personalized approach is very expensive, and if an individual is very sick, we often cannot get enough of her T cells to create CAR-T cells.

To overcome these shortcomings, various groups of doctors are genetically editing T cells so that T cells from one donor can be used to treat many people. 2015, Wasim Qasim The Great Ormond Street Child Health Institute at University College London and colleagues were the first to attempt this. Successfully treated a 1-year-old girl called Layla after all other treatments had failed.

This approach is now approved in the UK for leukemia patients involving another type of immune cell, the so-called B-cells. Alyssa’s leukemia is caused by her T cells, and if CAR-T cells are modified to attack other of her T cells, they will only kill each other.

Kasim’s team therefore made additional changes to CAR-T cells by knocking out the gene for the receptor that identifies them as T cells. Creating these CAR-T cells of her would require making four gene edits of her at once, which leads to yet another problem.

Conventional gene editing cuts DNA strands and uses the cell’s repair machinery to rejoin the ends. If you cut too many at once, the cells may die. Even if they survive, the wrong ends can be put back together, leading to large mutations that can turn the cell cancerous. increase.

So Qasim and his team used a modified form of the CRISPR gene-editing protein instead. DNAbut instead change one DNA letter to another, A technique called base editingAlyssa is the first person to be treated with base-edited CAR-T cells.

“I am very happy that she is in remission for the first time,” says Qasim.

“Base editing shows particular promise not only in this case, but also for inherited diseases,” he said. Robin Label-Badge at the Francis Crick Institute in London. Many other treatments are being developed, he says, including CRISPR base editing.

The only other existing trial involving this base-editing technique started in New Zealand in July this year. A company called Verve Therapeutics This approach could treat a genetic condition that causes dangerously high cholesterol levels.

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