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Turbocharged therapy

A new form of therapy that boosts the body's immune system to treat blood cancers is showing promise.

A new treatment that uses genetically modified cells to turbocharge the body’s immune system to fight cancer is an exciting field which is showing tremendous promise. However, there is still work to be done on chimeric antigen receptor (CAR) T-cell therapy: To have it used on solid tumours, to understand its side effects and to lower the cost of manufacturing.

This was the message relayed by Dr Lucas Chan, Chief Scientific Officer of Stem Med, to doctors at a Continuing Medical Education talk organised by Parkway Cancer Centre.

The therapy uses T-cells that have been modified in the laboratory to recognise cancer cells. T-cells are a kind of white blood cell that recognise and attack viruses and bacteria they find in the body. In the case of CAR T-cells, specific proteins that can recognise and engage cancer cells are attached to the T-cells, which are then given to the patient. These modified T-cells can then identify and kill their intended target.

In his talk, Dr Chan said that there is now a school of thought that people get cancer all their lives but that most of the time, the body’s immune system is able to fight it off. However as people age, their bodies get exposed to various toxins and chemicals over time and this depletes the immune system. Because the immune system has weakened so much, the body is no longer able to fight off the cancer cells.

CAR T-cells are able not only to help the immune system recognise cancer cells, but also to reactivate dormant or weakened T-cells to go into potent anti-cancer killing mode.

According to Dr Chan, there is now very positive data on the use of CAR T-cells on blood tumours such as B-cell acute lymphoblastic leukaemia (ALL), high grade B-cell lymphoma and multiple myeloma.

“There’s now very good clinical evidence to show that the field is moving forward,” he said. “We are seeing things that we couldn’t imagine 10 or 20 years ago. It’s a very exciting time.”

That said, CAR T-cell therapy is not a silver bullet against cancer. Currently, it has better results with liquid tumours than solid tumours, he noted.

Even with blood tumours, CAR T-cell therapy is not a straightforward solution as it comes with some side effects. “There is still a lot that we don’t know,” he said.

Another issue with CAR T-cell therapy is that it is not easy to manufacture. Kymriah, the first CAR T-cell drug approved by the United States Food and Drug Administration, takes between 15 and 22 days to make. “It is a very, very complex manufacturing procedure. It is not easy to do,” he said.

After getting blood from a patient or donor, the T-cells need to be isolated, purified and activated. These then need to be cultured so as to increase their number before infusing into the patient by using a genetically re-engineered virus.

“We hijack the virus, basically taking away all the pathogenic genes. This re-engineered virus doesn’t cause diseases, it’s just a shuttle carrier.”

Throughout the process, strict quality control is needed, and everything is tested before the CAR T-cells can be infused into the patient. “T-cell engineering may sound quite scary but in fact, if you understand the tests that go into examining how these therapies work, it is very, very safe,” he said.

He noted that this particular design had been used worldwide in hundreds of studies involving close to a thousand patients and there have not been any issues related to using the virus as the delivery vehicle for the therapy.

One consequence of the complex manufacturing process is that it adds to the cost of therapy.

However, Dr Chan was optimistic that over time, new technology would emerge to simplify the manufacturing process so that costs would come down and more people would be able to afford it.