StemCell Therapy

The biggest gains from these new tools have been in the treatment of melanoma, the cancer Australians suffer from more than anybody else, and non-small-cell lung cancer, the cancer that kills more Australians than any other.

Says Darren Saunders, a UNSW cancer researcher: "The way my clinical colleagues describe it to me is (that it's) the biggest transformation in the way we treat cancer in their careers."

"Without immunotherapy, I'd be a dead man": Warren Penna has seen promising results for the treatment of his melanoma. Credit:Chris Hopkins

It has made an enormous difference to patients who might otherwise have given up hope.

Warren Penna first noticed something was amiss when a large freckle on his right shoulder started to change shape. Then it darkened and began to bleed. The retired horticulturist went to a number of specialists before he was finally diagnosed with melanoma in 2014.

He had the cancer removed from his shoulder at The Alfred, but earlier this year, the 54-year-old Footscray man was diagnosed with throat cancer. As specialists conducted scans of his body, they discovered melanoma tumours in his lungs, liver, armpit and brain.

"When I saw the scans I was certain a dead man," Mr Penna said.

Doctors decided to target the melanoma first and the last eight months have been a blur of radiation treatments and surgery.

But it is the immunotherapy that Mr Penna is undergoing at Peter MacCallum, which involves fortnightly injections of antibodies Nivolumab and Ipilimumab, that has garnered the most remarkable results.

In a matter of months, the largest tumour in his lung has shrunk from 4.5 centimetres to 2 centimetres and specialists remain optimistic. His immunotherapy treatment will continue until mid 2022.

"It can be really tough at times because you are constantly thinking about your own mortality," Mr Penna said.

"But I feel so incredibly grateful I am able to get this treatment here in Australia and that is available on the Pharmaceutical Benefits Scheme, because I have no doubt I would be dead right now without it."

Immunotherapy is known for its severe side-effects and Mr Penna, who is also due to start radiation next week for his throat cancer, struggles with overwhelming fatigue and sometimes breaks out in a rash.

"I count myself very lucky though because so many others have really significant side-effects like diarrhoea and nausea," he said.

Cancer develops when a normal cells DNA mutates; often this is because it was exposed to a carcinogen like sunlight, but sometimes there is no cause at all. Just bad luck.

Our immune system is designed to sniff out and kill these mutated cells, but sometimes, the DNA mutation changes the cell in a way that makes it invisible to our immune system. Unchecked, the cell multiplies into a lethal tumour.

For the past 200 years, our treatments for cancer have been crude: surgery to remove the tumour; radiation to kill it; and broad poisons that kill the cancer but often the patient as well.

And then, almost overnight, everything changed.

In the '80s and 90s, scientists discovered immune checkpoints, tiny molecular flags that cells run up to mark them as friendly, so the immune system does not kill them.

They then discovered some cancers were covered in these flags, making them completely invisible to the immune system.

What if, the scientists thought, you could get rid of those flags?

"Initially, people were pretty sceptical of this idea. It was pretty unpopular," says Professor Doug Hilton, head of the blood cancer lab at the Walter and Eliza Hall Institute.

Independently, other labs had developed monoclonal antibodies. These are human immune molecules, made by cloned human immune cells living in a laboratory dish and specifically engineered to stick to a certain part of a cell.

With a tweak, the antibodies could gum over the checkpoints on cancer cells. Suddenly, they were visible to the immune system, which killed them.

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The first immune checkpoint inhibitor, the skin cancer drug Yervoy, was approved in Australia in 2011. Lung cancer drug Keytruda which Professor Hilton labels as one of the most important cancer medicines of the decade was approved four years later, and came on the Pharmaceutical Benefits Scheme at the start of December 2019.

"They have been absolutely transformative," says Professor Thomas.

A 2015 review of clinical trials of Yervoy for melanoma found more than 20 per cent of those treated were alive 10 years later and showing no sign of the disease. Before the treatment, the long-term survival rate was less than 10 per cent.

Keytruda treatment has led to complete remission for 22 per cent of patients with Hodgkins lymphoma in one clinical trial; in another, it cut risk of death by 40 per cent compared to conventional chemotherapy.

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Importantly, the effect of the checkpoint inhibitors appears long-term. Even after therapy stops, the immune system is still capable of spotting and killing any new cancers that arise.

"It appears to be a cure for some individuals," says Professor Thomas.

In 2011, as everyone was celebrating Yervoys success, word started to filter out about remarkable results in Philadelphia.

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An American team had completely cured a seven-year-old of a lethal childhood cancer leukaemia, using a new treatment called CAR-T.

That child, Emily Whitehead, is now 14. The cancer has not returned.

CAR-T works in reverse to checkpoint inhibitor therapy. A patients own immune cells are drawn from the blood and placed in a test tube.

A genetically modified virus is used to edit the DNA of those immune cells, giving them the ability to seek and kill the patients tumour.

When CAR-T works, it works extraordinarily well. One clinical trial led to the complete eradication of cancer in more than half the study participants.

Most excitingly, if the technique works, it could be used for almost any form of cancer. All the doctors would need to do is to tweak the T cells DNA to target the cancer in question.

The challenge, says Dr Saunders? "At the moment it costs half a million dollars per patient."

This is the next step. Bringing down the cost of immunotherapy, while also continuing clinical trials to see what other cancers it will work on.

But for the first time, a durable cure for cancer actually seems within our grasp.

Liam is The Age and Sydney Morning Herald's science reporter

Melissa Cunningham is The Age's health reporter.

Read this article:
'Scarily like a cure': the decade that revolutionised our fight with cancer - The Age

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