Patients with common but difficult-to-treat blood cancers may benefit from a treatment that reprograms the immune system to fight the disease.
Chimeric antigen receptor (CAR) T-cell therapy involves collecting infection-fighting white blood cells, known as T cells, from patients through a drip.
These are modified for five weeks in a laboratory, causing them to produce a cancer-fighting protein (CAR), creating CAR T cells. They are then put back into the patient via an IV infusion, where they seek out and attack cancer cells.
The therapy was previously only available on the NHS for certain blood cancer subtypes, but as part of a pivotal UK clinical trial, it is being tested in a broader group with common forms of the disease. It could throw a lifeline to those who, until now, have faced an uncertain prognosis.
TEST SUCCESS: Robin Edwards, 66, with her two grandchildren
“I can’t say I’m cured, but there are no signs of cancer at this time,” Mr. Edwards said after his successful CAR-T cell therapy.
Blood cancers affect blood cells and include leukemia, lymphoma, myeloma, and nearly 100 other forms. Collectively, there are more than 41,000 new diagnoses each year. Approximately a quarter of a million people are living with these diseases in the UK.
Blood cancer is also the most common cancer in children, with 500 children under the age of 15 affected each year.
Previously, CAR T-cell therapy has been offered to children with B-cell acute lymphoblastic leukemia and adults with diffuse large B-cell and mantle cell lymphomas, collectively affecting approximately 6,000 patients per year.
It is now being tested in patients with two other types: B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia, which together affect nearly 19,000 people each year.
Most patients with these cancers are successfully treated with chemotherapy and other drugs, but around a quarter have what’s known as refractory disease, meaning they don’t respond or relapse within two years.
The trial, led by the NHS Foundation Trust at University College London Hospitals (UCLH), offers CAR T-cell therapy to these groups. If it’s successful, doctors hope it will be widely used.
Trial investigator Professor Claire Roddie, a consultant haematologist at UCLH, said: “We found that CAR T can put patients with certain blood cancers into long-term remission.” We want to replicate this in other groups, offering hope to more patients.’
Speaking exclusively to The Mail on Sunday, the UK’s first chronic lymphocytic leukemia patient to receive the treatment revealed that he is now free of the disease after just two infusions of CAR T cells.
Robin Edwards, 66, from Buxton in Derbyshire, was diagnosed a decade ago after visiting his GP complaining of a swollen neck. They gave him chemotherapy and immune-stimulating drugs, which stopped the progression of the cancer.
However, in 2021 he began to deteriorate and was offered CAR T cell therapy as part of the trial. She had her infusions in May of that year. The treatment was successful and her consultants have told her that she is now in full remission.
He said: ‘This is brilliant news. I have two grandchildren, ages three and five, and I feel like I’m going to see them grow.
“I can’t say it’s cured, but there are no signs of cancer at this time.”
‘We found that CAR T can put patients with certain types of blood cancers into long-term remission. We want to replicate this in other groups, offering hope to more patients,” said trial investigator Professor Claire Roddie (pictured), a consultant haematologist at UCLH.
A trial, conducted by the NHS Foundation Trust of University College London Hospitals (UCLH), offers CAR T-cell therapy
CAR T-cell therapy was approved in the UK in 2018, but it has its drawbacks. A significant proportion of patients experience side effects, including cytokine release syndrome, in which the immune system becomes overactive, causing disease. Some need to be admitted to intensive care.
In other patients, the infused CAR T cells did not “take up,” and disappeared from the bloodstream.
The trial is using a new type of CAR T cell, genetically modified in a different way. Experts say that, thanks to this, they are overcoming these two challenges.
Dr Martin Pule, who leads the CAR T cell program at University College London, said: “A large focus of our work has been on minimizing the toxicity associated with CAR T therapy and maximizing the persistence of CAR T cells. in the body”.
When CAR T cells attach to cancer cells, they not only attack but also multiply, producing more cancer-fighting CAR T cells. ‘The proteins in CAR T cells act as a homing device, allowing them to seek out and attack cancers,’ says Professor Roddie.
“In early versions of the treatment, CAR T cells attached themselves for long periods of time, causing the immune system to overreact in some patients. We have now engineered a protein that binds to T cells for just a few minutes instead of hours.
“We hope this protects against side effects, but it may also create a more sustained production of cancer-killing T cells.”
In an earlier study, patients continued to make cancer-fighting CAR T cells years after receiving treatment. Professor Roddie said: ‘Eight of the original 20 participants in that trial are still in remission.
“Four out of five cases of chronic lymphocytic leukemia in the new trial are now in remission, the longest in 15 months.”
- For information about the trial, conducted by the UCLH NHS Foundation Trust and UCL, in collaboration with the National Institute for Health Research and UK-based CAR T cell therapy company Autolus Therapeutics, visit cancerresearchuk.org and search ‘ALLCAR19’.
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