Cancer patients to have immune cells changed with controversial technique


  • Trial is to be carried out on cancer patients at a hospital in Chengdu, China
  • Immune cells will be modified using CRISPR-Cas9 gene editing technology
  • The edited cells will then be reinjected back into the patients blood stream 
  • This may help the immune cells to recognise tumour cells in the patients

Richard Gray for MailOnline

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The world’s first clinical trial that will inject humans with genetically modified cells created with a ground-breaking DNA-editing technology is set to start next week.

Oncologists at Sichuan University’s West China Hopstial in Chengdu have been given approval to begin the tests with cells modified using the CRISPR-Cas9 gene-editing technique.

It is hoped it might provide a new treatment against cancer for patients who have not responded to chemotherapy or radiation therapy.

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The trial will use the CRISPR-Cas9 gene editing technique to alter T cells from the patient’s own immune system so they will target lung cancer in the patients (microscopy image of lung cancer cells pictured)

The researchers will extract immune cells known as T cells from the blood of the patients taking part in the trail and use CRISPR-Cas9 to knock out a gene in the cells.

This will disable a regulatory mechanism in the immune cells that prevents them from normally attacking other cells in the body.

WHAT THE TRAIL WILL DO 

The researchers will extract T cells from the blood of patients taking part in the trail.

A gene coding for a protein called PD-9 will be knocked out in the cells using CRISPR-Cas9.

The technique uses tags and an enzyme to cut DNA in a precise place, allowing small portions of a gene to be removed.

This turns off the gene for PD-9, which will mean the T cells will loose some of the regulation that stops them from attacking cells belonging to the human body.

These edited cells will be multiplied before being injected back into the patient.

Researchers hope they will then home in on the cancer and destroy it.

However, there are concerns the cells could become overactive and mount an immune response against healthy tissue too. 

The scientists hope that when these edited cells are reintroduced back into the patient’s bloodstream they will home in on the cancer and destroy it.

It comes as several groups in the United States have also been given approval to carry out gene-editing trails in humans.

Last month the US National Institutes of Health gave approval for a project that will use a similar approach in a trial involving 18 patients with several different types of cancer.

However, this trial also requires approval from the US Food and Drug Administration before it can go ahead.

In the Chinese trial, the trail will focus on patients who have metastatic non-small cell lung cancer where other treatments have failed.

Lu You, an oncologist at Sichuan University who is leading the study, told Nature: ‘Treatment options are very limited.

‘This technique is of great promise in bringing benefits to patients, especially the cancer patients whom we treat every day.’

CRISPR-Cas9 is based on a gene-editing technique used by bacteria to help them remove sections of DNA introduced by viruses that infect bacteria, known as phages.

CRISPR-Cas9 is a technique that borrows from the way bacterial cells defend themselves against infections by viruses known as phages. The Cas9 enzyme complex (green and grey in picture above) uses a tag (shown in red) to precisely target and cut DNA so that a section can be removed to silence a gene

Small chemical tags are used to get an enzyme to cut DNA in a precise place and ‘snip out’ a small piece of DNA.

This can be used to turn off specific genes in an extremely precise manner that has not been available using previously less accurate gene editing techniques.

However, scientists now need to prove the technique can be used safely in patients before it can be used more widely and these initial tests will aim to show it does not harm those being treated.

Future trials will then have to assess how effective the technique is compared to other types of treatment.

In the Chinese trial the researchers will use CRISPR-Cas9 to target a gene that produces a protein called PD-1 in T cells.

This protein usually helps to regulate the T cell’s ability to launch an immune response and prevents it from attacking healthy cells belonging to the body.

By knocking out this gene with great accuracy, the researchers believe it will be possible to increase the immune response against cancerous cells, which are often overlooked by the immune system as they are made of the same cellular material as the rest of the body.

WHAT IS CRISPR-CAS9 AND HOW IS IT USED?

CRISPR-Cas9 is a tool for making precise edits in DNA, discovered in bacteria. The acronym stands for ‘Clustered Regularly Inter-Spaced Palindromic Repeats’. 

The technique involves a DNA cutting enzyme and a small tag which tells the enzyme where to cut. By editing this tag, scientists are able to target the enzyme to specific regions of DNA and make precise cuts, wherever they like.

It has been used to ‘silence’ genes – effectively switching them off. 

When cellular machinery repairs the DNA break, it removes a small snip of DNA. In this way, researchers can precisely turn off specific genes in the genome.

The approach has been used previously to edit the gene called HBB responsible for a condition called ?-thalassaemia.

Previous trials have attempted to block PD-1 using antibodies but it is hoped silencing the gene that produces it will be more effective.

Timothy Chan, an immunotherapy expert at Memorial Sloan Kettering Cancer Centre in New York, who is not involved in the trial, said the gene editing technique promised to be a more powerful way of targeting cancer than with the approach using antibodies.

The trial is being conducted with Chinese biotechnology company Chengdu MedGenCell.

China has been pushing ahead with gene editing technology and is leading the world in using CRISPR techniques after being the first to use it to edit human embryos and in monkeys.

However, it has raised some fears that they may be moving faster than is perhaps safe.

Dr Chan said there was a chance the CRISPR-Cas9 editing of T cells could induce an excessive immune response that could lead to them attacking healthy tissues in the patient’s body.

He told Nature: ‘That will be a concern.’

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