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CAR T-cell therapy: A revolutionary new approach to fighting cancer

The Malaghan Institute of Medical Research in Wellington is gearing up for a clinical trial of CAR T-cell therapy, which harnesses the body’s immune system to fight cancer.

David Downs thought he had a mild case of the flu. But it turned out the businessman, writer and comedian had a form of blood cancer, non-Hodgkin’s lymphoma, which resisted a year of chemotherapy and did its best to kill him. He wouldn’t be around today if he hadn’t managed to get on to a clinical trial for a revolutionary new treatment, CAR T-cell therapy.

Yes, he was lucky, but that luck involved the support of many people, who helped raise funds for him to travel from Auckland and pay for the immunotherapy treatment at Massachusetts General Hospital in Boston – about NZ$400,000 so far.

CAR (chimeric antigen receptor) T–cell therapy harnesses the body’s immune system to fight cancer. White blood cells are taken from a patient, then their infection-fighting T-cells are isolated and modified in the lab so they can recognise cancer cells. The T-cells are then infused back into the patient to seek and destroy the cancer cells.

In the UK, a second-generation version of the treatment is available for some children with leukaemia and adults with blood cancer. In the US, it is Food and Drug Administration-approved for use against some blood cancers. But it has not been available in New Zealand. Wellington’s Malaghan Institute of Medical Research aims to change that. It is gearing up for a clinical trial of a third generation of the therapy that researchers hope will be more effective, affordable and easier to deliver.

Cancer survivor David Downs. Photo/Supplied

The ambitious trial will cost millions, but research director Professor Graham Le Gros says it is vital for this country to be involved in the development of what may prove to be a cure for many other types of cancer.

“We have got to have people skilled in the art,” says Le Gros. “It can’t only be the domain of the big drug companies.”

The independent biomedical institute believes it can deliver the therapy for less than the cost of chemotherapy.

Breaking new ground isn’t without risks. Anything that involves manipulating the immune system can create problems. Neurological symptoms, such as headaches, confusion and delirium, are among the list of side effects so far. And a severe immune overreaction, or cytokine storm, has the potential to be life threatening.

Le Gros compares where CAR T-cell therapy is today with the early forms of penicillin.

“No scientist likes to say it, but our knowledge of the immune system is rudimentary at best. We need to understand more. We know we’ve got 50 different types of T-cells, for instance. With CAR T-cell therapy, we modify all of them. No one knows yet which is the right cell. There may be only one or two.”

There is optimism that the new therapy can be tailored to be effective at treating solid tumours, not only liquid cancers, as is currently the case. Le Gros sees the potential for it to be used eventually for less-lethal but chronic conditions, such as arthritis or Crohn’s disease.

Graham Le Gros. Photo/Supplied

“Over the next 50 years, as we learn to direct the immune system to control itself, there are going to be a lot of exciting developments.”

The institute has partnered with Hunan Zhaotai Medical Group in China to develop the improved therapy. It was Kiwi expertise at growing human cells in cultures that attracted this overseas interest. But raising enough to fund the research and development remains a challenge.

The Government has committed $4.5 million over five years and David Downs has pledged to raise a million. He is taking on public-speaking engagements and has self-published a book, A Mild Touch of the Cancer (Bakita Books, $39.99), with plans to donate the profits.

“I was lucky and I want more people to get the same opportunity,” says Downs, who has been in remission for a year and regularly returns to Boston for checks. “Every time I go, they say I’m in fine health.”

More than half the patients treated as part of the trial have not responded as successfully and the challenge is to work out why. And researchers also don’t yet know about the long-term prospects – one of the conditions of being accepted for the Boston trial was Downs agreeing to continue to be monitored for the next 20 years.

“Before this, my chance of beating cancer was 5%,” he says.

This article was first published in the August 17, 2019 issue of the New Zealand Listener.