Experimental CRISPR approach holds promise towards aggressive leukemia

A 13-year-old girl with leukemia who didn’t respond to other treatments now has no detectable cancer cells after receiving a dose of immune cells genetically edited to attack cancer

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A teen with aggressive leukemia is now undetectable cancer Cells after becoming first person to receive novel treatment CRISPR technology called base editing. However, it is unknown whether she will remain healthy in a few years.

The 13-year-old girl, Alisa, did not respond to other treatments. As part of the trial, she received doses of immune cells from a donor that had been engineered to attack cancer. After 28 days, tests showed that she was in remission.

“This is remarkable, although it is still a preliminary result that will need to be monitored and confirmed in the coming months,” said Robert ChiesaA doctor treating Alyssa said in a statement issued by Great Ormond Street Hospital in London.

Leukemia is caused by Immune Cells in the bone marrow proliferate out of control.It’s usually done by killing all the bone marrow cells with chemotherapy and then transplant. This is successful in most cases. If that fails, doctors can try something called CAR-T therapy.

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

Initially, all CAR-T treatments involved removing a person’s own T cells, modifying them and replacing them in that individual. If T cells from another person are used, they attack every cell in the recipient’s body. This personalized approach is expensive, and when a person is very ill, it is often impossible to obtain enough T cells to create CAR-T cells.

To overcome these shortcomings, different groups of doctors have been genetically editing T cells so that T cells from a single donor can be used to treat many people. In 2015, wasim kasim and colleagues at the Great Ormond Street Institute of Child Health at University College London were the first to try this, Successfully treated Layla, a 1-year-old girl who had failed all other treatments.

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

So Qasim’s team made additional changes to the CAR-T cells by knocking out the receptor gene that recognizes them as T cells. Creating these CAR-T cells required four simultaneous gene edits, which posed another problem.

Traditional gene editing involves cutting strands of DNA and relying on the cell’s repair machinery to rejoin the ends. Cells sometimes die when a large number of cuts are made at once. Even if they survive, the erroneous ends can recombine, causing major mutations that can turn cells cancerous. The more gene editing done, the more likely it is that this will happen.

So Kassim and his team turned to a modified form of the CRISPR gene-editing protein that doesn’t cut DNAbut changing one DNA letter to another, A technique called base editing. Alyssa is the first person to receive base-edited CAR-T cell therapy.

“We’re so happy she’s in remission for the first time,” Kassim said.

“Base editing is particularly promising, not only in this setting, but for genetic diseases,” said robin lovell badge at the Francis Crick Institute in London. Many other treatments involving CRISPR base editing are in development, he said.

The only existing trial involving this base editing technique was conducted in New Zealand in July this year.A company called Verve Therapeutics wants to demonstrate This approach could treat genetic disease that causes dangerously high cholesterol levels.