麻豆传媒

ONE of the most amazing things about the immune system is how hard it works without you even being aware. It not only fights off bacteria and viruses every day, it also kills off most cancers long before they become a threat. But sometimes cancers manage to dodge the immune system 鈥� and a number of cancer therapies rely on restoring its effectiveness. An emerging star is CAR T-cell therapy, which has produced dramatic results for some cancers when all the usual treatments have failed.

This incredible technology relies on T-cells, immune cells that patrol our body, killing infected or cancerous cells. T-cells detect their targets with a receptor that protrudes from their surface and binds to a target protein, or a displayed fragment of a protein, on the outside of other cells. What this means is that if you add the right receptor to T-cells, you can make them target anything you want, including a cancer.

To achieve this, a person鈥檚 own T-cells are extracted and genetically modified to express a 鈥渃himeric antigen receptor鈥�. This artificial receptor is made up of three proteins, one that recognises the cancer cell target and two that boost the T-cells鈥� activity.

Doctors multiply these cells and return them to their owner, where they seek out and destroy cells that have the target protein.

With a few of the first people treated still remaining free of cancer a decade later, it can now be said that, in some cases, CAR T-cell therapies can cure advanced cancers.

Unfortunately, this approach isn鈥檛 a magic bullet. For starters, the immune attack on cancer cells it prompts can trigger potentially fatal side effects. What鈥檚 more, CAR T-cells only work against blood cancers, not solid tumours, and only in a minority of people.

But there is hope. The technique is being improved. One big issue is that having to use each individual鈥檚 own T-cells is extremely expensive, and with very ill people, it isn鈥檛 always possible to extract enough T-cells. Donor T-cells see every cell in the recipient鈥檚 body as foreign and start attacking them.

So, gene editing is now being used to knock out the genes involved in recognising cells as foreign, in addition to adding the receptor. These universal CAR T-cells can be used to treat many different people with the same cancers.

Leukaemia success

Another issue is that T-cells have an off switch on their surface called PD-1 to help prevent them attacking healthy cells. Some cancers thwart T-cell attacks by exploiting this switch. But if it is removed via gene editing, the T-cells can鈥檛 be deactivated.

With standard gene editing, there is a limit to the number of changes that can be made. This is because each edit requires cutting DNA, which can kill cells or result in major mutations. But the latest CRISPR gene-editing tools don鈥檛 cut DNA and so allow more changes to be made safely.

This approach was used last year to treat T-cell leukaemia for the first time. The 13-year-old who received the treatment had aggressive leukaemia that hadn鈥檛 responded to any other therapy. Twenty-eight days later, tests revealed she was in remission.

Other teams are introducing even more ambitious changes to CAR T-cells in the hope of making them effective against solid tumours too. The use of CAR T-cells for treating infections by pathogens such as HIV and hepatitis C is also being explored. Furthermore, CAR T-cells are being used to treat autoimmune diseases by killing off the rogue immune cells responsible. Last year, a team in Germany reported that five people with lupus have remained free of the disease since being treated this way.

Genetically engineered immune cells are going to be a big part of our future. It is a future that looks very bright indeed.