Malaghan Institute researchers are trying to find a CAR T-cell therapy more effective than current ones – but also safer, and affordable – that can be introduced to our healthcare system.
Malaghan Institute researchers are trying to find a CAR T-cell therapy more effective than current ones – but also safer, and affordable – that can be introduced to our healthcare system.
A breakthrough Kiwi-made cancer therapy has moved closer to market, with its developers entering a multimillion-dollar deal with a global drug giant.
The clever biotech at the heart of the deal between Wellington Zhaotai Therapies and India-based pharma company Dr Reddy’s Laboratories is now undergoing a first-of-its-kind medical trial inNew Zealand, targeted at certain types of lymphoma.
That’s a new generation of CAR T-cell therapy, where, in this case, a patient’s own immune or T-cells are genetically modified to recognise and destroy their cancer.
In New Zealand, scientists have been exploring its potential since Wellington’s Malaghan Institute of Medical Research formed a joint venture with China’s Hunan Zhaotai Medical Group six years ago.
They’ve been developing a new CAR T-cell construct which appears to produce stronger anti-cancer activity than existing forms of the therapy – potentially offering patients more effective treatment.
While now a standard therapy overseas for types of relapsed lymphoma, leukaemia and for myeloma, CAR T-cell therapy is not yet available as a funded treatment here in New Zealand.
As it works in a very different way to conventional chemotherapies and radiotherapies, it could often prove much more successful for patients whose blood cancer hadn’t responded well to other treatments.
For Kiwi businessman David Downs – once given mere months to live after 12 rounds of chemotherapy failed to subdue his non-Hodgkin lymphoma – travelling to the US to receive CAR T-cell therapy proved a life-saving decision.
Here, meanwhile, Malaghan researchers have been trying to find a CAR T-cell therapy more effective than current ones – but also safer, and affordable – that could be introduced to our healthcare system.
Current CAR T-cell therapies happen to come with some notable limitations, including cases of severe side effects brought on by over-activation of the immune system.
Building on second-generation therapies used overseas, their treatment added a new gene segment called TLR2, which has been shown to alter the effect of the CAR T-cells.
Source / Malaghan Institute
Since the “Enable” trial began in late 2019, the team had been enrolling patients with specific types of lymphoma from across the country, manufacturing CAR T-cells at the Malaghan Institute, and treating them in Wellington.
In January, the team treated their 21st and final patient in the dose escalation part of the trial.
Preliminary clinical data also suggests an improved safety profile, with fewer side effects than competing CAR T-cell treatments.
At this point, Enable was still a phase-one trial – which meant it was the first time this type of CAR T-cell has been given to people – with results due later this year.
Because CAR T-cell treatment is both a gene and personalised cellular therapy, the team had to work through the complex process of manufacturing CAR T-cells themselves, in what’s one of the world’s tightest regulatory environments for genetic research.
After gaining extensive approvals to make the cells and run the trial, hospital safety protocols needed to be set up to monitor and manage any patient side-effects.
Remarkably, the team was able to progress the trial throughout the disruption of the Covid-19 pandemic – even obtaining special exemptions for patients to travel during lockdowns.
It was hoped results from the phase-two trial – expected to get under way next year – would lead to approval for routine use of the treatment here.
Wellington Zhaotai Therapies executive director Peter Lai said the new agreement with Dr Reddy’s gave the company exclusive licence to trial and commercialise the construct in India.
But it also signified a strategic partnership that could potentially extend to other countries and other cell therapies, he said.
“To develop a product through clinical trials to global licensing is no mean feat,” he said.
“This is a significant milestone for a New Zealand biotech.”
Dr Murali Ramachandra, chief executive of Dr Reddy’s wholly-owned subsidiary Aurigene Oncology, said the hope was to bring an advanced, third-generation CAR T-cell treatment option to India.
“The available clinical results suggest a superior safety profile,” he said.
“Apart from being an effective treatment, single infusion would mean reduction in the length of hospital stay, thereby delivering additional benefits to the patient.”
