Biotech

New data bolsters Prescient Therapeutics’ focus on next generation CAR-T cell therapy for cancers

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By Lorna Nicholas - 
Prescient Therapeutics PTX ASX next generation CAR-T cell therapy cancer

Findings of active CAR-T cells in leukemia patients a decade on suggests there is a “huge opportunity” for next generations of the technology, which Prescient is at the forefront of developing.

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New data published in the science journal Nature has supported clinical stage oncology company Prescient Therapeutics’ (ASX: PTX) use of next generation cell therapy platform OmniCAR, which harnesses a patient’s own immune system to fight cancer and other illnesses.

On a basic level, CAR-T therapy involves collecting and using a patients’ own immune cells to treat their individual malignancy.

CAR-T is an adoptive cell transfer and is one of several types of immunotherapy approaches. However, CAR-T is the most advanced.

The US Food and Drug Administration approved two CAR-T cell therapies in 2017 – one for treating children with acute lymphoblastic leukemia and the other for adults with advanced lymphomas.

An early leader in the CAR-T cell field, Dr Renier Brentjens says the therapy is the equivalent of giving patients a “living drug”.

The backbone of existing CAR-T therapy is T cells, which are often referred to as the immune system’s workhorses.

T cells are critical in orchestrating the immune response and killing infected cells.

Treatment involves drawing blood from a patient and harvesting the T cells. Using a disarmed virus, T cells are then engineered to produce chimeric antigen receptors (CARs) on their surface.

Promising new data

Professor Carl June has led a series of clinical trials testing this therapy – mostly in leukemia patients.

In trials, the CARs enable the T cells to recognise and attach to a specific protein, or antigen, on tumour cells.

When treating cancer, the T cells are engineered to express antigen-specific CAR. These antigen-specific CAR are multiplied in the laboratory into the hundreds of millions.

Dr June and his colleagues’ recently published data and commentary in Nature on two patients that underwent CAR-T therapy a decade ago.

The data indicates CAR-T cells are still active 10 years later in two patients with lymphocytic leukaemia who achieved complete remission in 2010.

Prescient sees this data as hugely encouraging as it looks to create the next generation CAR-T therapy that can bring these responses to more cancer patients across various malignancies.

A potential cure?

Commenting on the data, Prescient managing director and chief executive officer Steven Yatomi-Clarke said the company had tracked the patient remissions over the years “with great interest” particularly as they got “longer and longer”.

“What really drew the headlines around the world most recently is Professor June’s use of the word ‘cure’,” he said.

The term is controversial as it hasn’t been used before in the context of cancer.

“Instead, oncologists speak about delaying progression of disease (sometimes by small amounts); about improving the quality of life; and even improving rates of survival at five years after treatment.”

“But we’ve not dared to use the word ‘cure’,” Mr Yatomi-Clarke explained.

He said for an expert of Professor June’s “immense standing” the bold declaration of “cure” has reverberated.

“To basically look at this amazing data collected over 10 years and say, ‘if it looks like a cure and smells like a cure’, we can comfortably say now that CAR-T has at least some curative potential for leukaemia patients like those seen in this study.”

Just the start

Mr Yatomi-Clarke pointed out this was just the start for CAR-T therapy, with the technology already 10 years old and these trials beginning a decade ago.

“It makes you wonder what this next generation, which at the forefront of, might be able to do.”

Mr Yatomi-Clarke noted Prescient’s next generation technology is also from the same institute that pioneered the original technology – the University of Pennsylvania, along with input from Oxford University.

“I think it’s incredibly exciting that the first iteration has curative potential and it’s only going to get better. It’s only going to get cheaper.”

Barriers to existing CAR-T therapies

According to Mr Yatomi-Clarke one of the main barriers to existing CAR-T treatments is cost and the length of time to make it.

“At the moment, as wonderful as CAR-T is, it’s really expensive, it’s really slow, and it has some safety issues.”

He said because of these issues, it is reserved for certain blood cancers and very sick patients who are resistant to other treatment options.

Current CAR-T is not working in a myriad of other cancers and Mr Yatomi-Clarke says this is a “huge opportunity” for next generations of the technology.

“I think, ultimately, the whole field is working towards an end goal of being an off-the-shelf T-cell treatment.”

Mr Yatomi-Clarke cautioned the field was still “quite a way” from off-the-shelf products.

Next generation OmniCAR therapy

What Prescient is attempting to do with its OmniCAR therapy is solve these key challenges.

The company aims to make CAR-T therapy work better and be safer, with the therapies also made at scale and therefore more affordable.

“So, we can treat more cancers and access a lot more patients as you’re able to drive down the costs and make a safer product that works better.”

“People were talking a few years ago about developing nano robots that can be injected into humans and patrol your body for disease and cancer – well, that’s what this is.”

“Why reinvent the wheel? There’s over 3 billion years of evolution culminating in our bodies making these amazing immune cells – so just harness them,” he added.

The company’s OmniCAR technology has the potential to generate controllable and flexible CAR-T products to use against a variety of cancers.

These CAR-T cell therapies can be controlled post-infusion, re-armed and re-directed from one cancer antigen to another.

During Prescient’s pre-clinical research, the products demonstrated cancer killing activity and high potency.

Results showed OmniCAR cells begin antigen-direct killing of tumour cells in vitro as soon as they are armed.

Studies also demonstrated that OmniCAR cells could be re-armed and continue to kill tumour cells without loss of cytotoxicity, and that this technology can be used against numerous cancer antigens.

Looking ahead

Looking ahead to the next decade of technological advancement in the area, Mr Yatomi-Clarke said he “firmly believes” a lot more cancers will be treated far more successfully.

“I’m hoping that OmniCAR is front and centre of this cell therapy revolution, because it’s agnostic and can work with any binder and any type of immune cell.”

In the future, Mr Yatomi-Clarke said he saw a “patient-centric ecosystem”.

Samples would be taken from a patient’s tumour, then characterised. A doctor would then determine which binders match that cancer.

“They might say, ‘based on your cancer profile, we need OmniCAR binders one, three, and 10’ and put it on an OmniCAR cell.”

This would essentially be a customised therapy for a particular patient that is also controllable and effective.

“It’s a plug and play approach to cancer. And anyone with a binder or cell type can contribute to the ecosystem with OmniCAR at its heart.”

Beyond the realm of cancer

Mr Yatomi-Clarke pointed out that this treatment method could also be applied to other diseases including infectious and autoimmune ones such as rheumatoid arthritis.

“Autoimmune diseases are a close cousin of cancer in away – in terms of the way the body work.”

This presents a much broader market for Prescient’s technology beyond the realm of cancer.