The CAR T-cell therapy (Chimeric Antigen Receptor) has been billed as a radical new way to cure cancer.

But since the US FDA approved the first cell-gene therapy to treat leukemia in 2018, the technology has not really caught on in the mainstream.

So is there a place for CAR-T therapy within the wider immuno-oncology market?

According to the latest data from Grandview Research, the market is about to explode from US$1 billion in 2020 to US$20.3 billion by 2028, with two million patients in 10 years.

Australia is also starting to adopt the technology. Earlier this month, the government approved the use of Yescarta, a type of CAR-T cell therapy that’s used to treat patients with certain types of lymphoma — a form of blood cancer.

It’s expected up to 300 Australians per year will benefit from these therapies, which are available at selected public hospitals.

A handful of ASX-listed companies are also rapidly advancing their research into the T-cell therapy space.

Immutep (ASX:IMM) announced on Friday a patent grant in China for the use of its LAG-3 antibody molecules.

LAG-3 (or Lymphocyte Activation Gene-3) is a gene that codes a protein involved in the regulation of the immune system.

Immutep is currently studying how the LAG-3 immune control mechanism reacts with its lead drug, eftilagimod alpha.

Another ASX-listed company, AdAlta (ASX:1AD), has also just flagged its intention to enter the CAR-T space, signing a collaboration agreement with Carina Biotech last week.

AdAlta mainly focuses on its lead drug candidate, i-body AD-214, to treat fibrosis, and its entrance into CAR-T is a welcome boost for the sector.


How CAR-T therapy works

Stockhead caught up with AdAlta CEO, Dr Tim Oldham, to ask him how CAR-T works and what the current challenges are.

“CAR-T is all about reprogramming the body’s own immune system to fight cancer,” Oldham explained to Stockhead.

T-cells themselves are a type of white blood cells found naturally, which patrol the body for signs of disease.

T-cells do this by using the receptors found on their surface to latch on to antigens of cancer cells, which are then killed by injecting them with toxins.

The trouble is, cancer cells are smart and can avoid detection.

“The cancer cells are really good at hiding from the immune system by disguising themselves so the T-cells don’t recognise them,” Oldham said.

“And so our immune system doesn’t do a great job of tracking down cancer.”

What the CAR-T cell therapy does is to reprogram the T-cells to break through the cancer cells’ defences.

The first step of the process is to collect white blood cells from the patient’s blood using a procedure called leukapheresis.

When the white blood cells are removed and T-cells separated, they are sent to the lab which then genetically modifies the patients’ T-cells’ receptors to recognise the specific cancer.

“It’s essentially like putting on a GPS on the T-cells back into your body,” says Oldham.


Obstacles to mass adoption

According to Oldham, there are a few obstacles that need to be overcome before CAR-T therapies could really go mainstream.

Firstly, the therapy is currently only effective on blood cancers, and not on solid tumours.

“We’ve been really successful with blood cancers because it’s relatively easy to find tumour-specific antigens in blood cells,” explained Oldham.

Solid tumours on the other hand, are much harder for three reasons.

Firstly, there’s not as many tumour specific antigens known and the tumour cells don’t necessarily express them all, so it’s much harder to zoom in and target these solid tumour cells.

“The second problem is getting the T-cells into the solid tumour. With a blood cancer it’s easy because they’re all in the blood anyway.”

The third challenge with targeting solid tumours, Oldham explained, is that a tumour is an environment that’s designed to suppress the immune system to stop working.  And this just makes it much harder for CAR-T cells to find and penetrate solid tumours.

Oldham says AdAlta’s collaboration with Carina will potentially address all three problems.

“Our technology which we call i-bodies will enable us to really target the solid tumours,” he said.

Oldham explained that AdAlta’s i-bodies are the “next generation antibodies” that are genetically modified and are approximately one-tenth the size of monoclonal antibodies.

“The Carina technology meanwhile, will overcome the local penetration of the tumour in the immuno-suppression, and that combined with our i-bodies will give us a new way to hit CAR-T on solid tumours.”

The other obstacle to mass adoption of CAR-T is the cost of these therapies. At the moment, prices are in the vicinity of US$400,000 for a single dose.

“This is because every dose has to be made specific for each patient,” Oldham said.

Another challenge is the safety, and there has been examples where patients have experienced really severe adverse events.

“The safety issue is currently significant, but equally you’re looking at a disease that’s going to kill someone anyway.”

Other ASX companies that focus on CAR-T therapies include Chimeric Therapeutics (ASX:CHM), Prescient Therapeutics (ASX:PTX), and Imugene (ASX:IMU).