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Parkway Cancer Centre’s Dr Lim ZiYi talks about how the use of genetically modified T-cells offers hope for the treatment of blood cancers and, in future, perhaps solid tumours as well.

Cell therapy is a critical component of the fight against cancer in the future. In fact, it has already been shown to work with blood cancers and research is now underway to see if it will work on solid tumours as well.

That was the message from Dr Lim ZiYi, a senior consultant in haematology who spoke at a cancer seminar organised by Channel NewsAsia and Parkway Cancer Centre.

Cell therapy is one type of immunotherapy which involves using the body’s own immune system to fight cancer.

With cell therapy, scientists and researchers use CAR T cells to locate and kill cancer cells. T cells are part of the immune system and develop from stem cells in the bone marrow. They are a kind of white blood cells which help the body fight off infections. They also have the ability to kill cancer cells.

CAR T cells are T cells that have been genetically engineered to produce receptors on their surface called chimeric antigen receptors (CARs). These special receptors allow T cells to recognise and attach themselves to a particular protein, or antigen, on tumour cells.

“Once the cancer is hit, the T cells are triggered to multiply at a very rapid rate so effectively creating a nuclear bomb to kill the cancer,” said Dr Lim.

He recounted the dramatic story of Layla Richards, a little girl in London who was diagnosed with infant acute lymphoblastic leukaemia (ALL) when she was just three months old back in 2015. It was an extremely aggressive form of leukaemia that resisted conventional cancer treatment like chemotherapy.

“The parents were ready to give up. They had no more options. At that stage, they went to see a specialist who had just developed an experimental form of cell therapy.

“And because there was nothing to lose, they said, ‘Let’s give it to her.’” At the time, the treatment had never been tried on humans.

“Her doctors gave her a small 1ml infusion of genetically engineered cells.” Nothing happened in the first three weeks but suddenly, in the fourth week, the leukaemia cells started to melt away.

“Spectacularly, over the course of a few months, the cancer burden on the body just disappeared. All this was from just 1ml of cells. This is the promise of cell therapy,” said Dr Lim.

Cellular therapy has side effects though. “When you kill the cancer with such ferocity, the chemicals that are released can make the patients quite sick,” he noted.

In earlier studies, some patients experienced multi-organ failures while others suffered from neurotoxicity (poisoning of the brain and nervous system). “One of the big challenges is how we can attenuate the treatments to make it as effective but safer for patients.”

Research on cell therapy has been going on for the past few years and so far, researchers have good data on blood cancers such as ALL and lymphoma. Now, they are beginning to get data on myeloma, another kind of blood cancer, he said.

Researchers now want to see if it works in solid tumours. Solid tumours are more common than blood cancers, so if cell therapy can work on solid tumours, the impact would be greater.

Another challenge is the cost of this treatment, which is around US$300,000. “We obviously need to get the cost down,” he said.

Dr Lim noted that Stem Med, the first private stem cell banking and cellular laboratory in Singapore, is looking at developing cell therapy. “We believe that doing it in Singapore, we could probably make it cheaper and more effective.” Singapore’s advantages are that it has “great regulations, great scientists and great access to healthcare”.

In August 2017, after Dr Lim spoke at the cancer seminar, the United States Food and Drug Administration approved Kymriah, the very first gene or cell therapy available in the US. Two months later, the FDA approved Yescarta, another gene therapy.

Kymriah was approved for certain paediatric and young adult patients with a form of ALL while Yescarta was approved to treat adult patients with certain types of large B-cell lymphoma who have not responded to or who have relapsed after at least two other kinds of treatment.

Written by Jimmy Yap