How an experimental therapy weaponised Nikola's failing immune system

Nikola Barac, 6, with his mother Fiona Stamenkovic and brother Milan outside Westmead Institute for Medical Research.  Photo: Jessica Hromas
Nikola Barac, 6, with his mother Fiona Stamenkovic and brother Milan outside Westmead Institute for Medical Research. Photo: Jessica Hromas

Nikola Barac's immune system has done him no favours. Leukaemia and rare genetic immunodeficiency disorder hyper IgM have left his small body defenceless against life-threatening infections.

"I'd have a heart attack every time he had bathwater in his mouth," his mother Fiona Stamenkovic said.

"I would use boiled water to brush his teeth. We had to be very careful."

When Nikola was four years old, and in spite of his family's constant vigilance, an ultrasound picked up the parasite cryptosporidium in his bile ducts and liver.

"It was just devastating," Ms Stamenkovic said.

"I knew what it meant. I thought his liver was going to fail and he would die."

Nikola received two bone marrow transplants from his younger brother, Milan, to fight the infection. It worked, but another insidious virus called cytomegalovirus had flourished in its place.

"The medication he needed was very toxic. It was horrible giving it to him [knowing it could cause him harm]," Nikola's mother said. This time the treatment didn't work.

In a last-ditch move, Nikola's doctors weaponised the very thing that had failed to protect him in the first place. He was given two rounds of genetically-modified T-cell immunotherapy grown in Westmead Institute for Medical Research (WIMR).

This time he was given the all clear.

"It's incredible. This thing has been a part of our lives for so long and now it's not. It's going to take a while to get used to it," Ms Stamenkovic said.

For the first time in Australia a clinical trial is paving the way for patients with leukaemia and lymphoma to access a potentially-life-saving immunotherapy treatment.

A team of researchers at WIMR and Westmead Hospital has been given the go ahead by the Therapeutics Goods Administration to conduct a phase 1 trial.

Launched on Tuesday, the CARTELL trial will recruit 20 leukaemia and lymphoma patients, children and adults, whose disease has returned despite having bone marrow transplants.

The chance of survival for these patients at five years is roughly 10 per cent.

Immunotherapy has become a promising new frontier in cancer treatment that harnesses the power of the immune system to find and attack cancer cells has yielded remarkable results in clinical trials overseas.

"The results have been incredible, there is no other way to describe it," said Professor David Gottleib, group leader of the Bone Marrow Transplant and Cell Therapies Group at WIMR and senior physician at Westmead Hospital.

"People have been blown away by the amazing response rates in people with leukaemia who had very few other choices," he said of the research field still in its infancy.

A small number of eligible Australian cancer patients have spent an estimated $500,000 - $700,000 to access treatment in US trials, on top of the cost of travel, hospital accommodation costs for themselves and their support people.

Professor David Gottlieb at the Westmead Institute of Medical Research

Professor David Gottleib at the Westmead Institute of Medical Research. Photo: Supplied

The exorbitant cost and limited trial places means the experimental treatment is beyond their reach for most patients.

"The long term goal is to make CAR T-cells affordable and widely accessible to Australian patients as quickly as we can," Professor Gottleib said.

"But there is still a long way to go before we can regard it as routine."

Trial participants will receive genetically modified donor T-cells fitted with chimeric antigen receptors (CARs) that can identify and kill cancerous leukaemic and lymphoma cells.

Published trials overseas have used a viral system to insert the receptors into the cells, stripping away the dangerous components of a virus. The exhaustive process to ensure the alter virus is safe costs hundreds of thousands of dollars.

But the method used in the Australian trial will bypass the viral delivery system, Professor Gottleib said.

"We essentially take two pieces of DNA and cut and paste the receptor into the DNA," he said.

"It means we'll be able to manufacture the cells quickly and more affordably."

The technique could reduce the cost of commercial T-cell treatment from roughly $300,000 to about $50,000, he said.

But it will need to be rigorously tested.

"We don't know the answer to the efficacy question. That's why we're doing the trials," Professor Gottleib said.

"But how you get the receptor into the cells, one has no reason to think the end results should be different," he said.

The researchers will be on high alert for side effects seen in trials overseas, including the potentially fatal cytokine release syndrome, in which the T-cells become overactivated and release inflammatory chemicals that damage healthy cells.

The treatment can also cause neurotoxicity that damages the nervous system, which can cause confusion, memory loss, convulsions and other cognitive dysfunctions.

"We'll definitely be looking for those sorts of problems," Professor Gottleib said.

The new trial is part of a series of trials conducted by the WIMR researchers, aimed at strengthening immunity to infection in cancer patients receiving chemotherapy and other toxic treatments.

They hope to apply for a second trial using participant's own T-cells to create the CARs among leukaemia and lymphoma patients who have not responded to chemotherapy.

The CARTELL trial is expected to run for 18 months to two years.

Patients who may be interested in participating in the trial should speak to their GP or specialist about their suitability.

This story How an experimental therapy weaponised Nikola's failing immune system first appeared on The Sydney Morning Herald.