The pandemic turned the global focus on medicine, and while it made some pharmaceutical companies a lot of money, it also produced many armchair experts who suddenly had a lot to say about the health sciences, including the immune system and how it works.
With investor attention trained on this sector by global events, now seems like the right time to talk to experts about new frontiers in medicine.
One of the great breakthroughs in biotechnology in recent years has been the realisation that we can harness the power of the immune system to target some of the thorniest clinical problems of our time.
Vast global market
In biotechnology, one of the biggest motivators is unmet need. In 2020, we saw what happened when scientists were presented with a very large and unexpected unmet need – to scramble a vaccine for COVID-19.
But before there was COVID-19, there was cancer, and unfortunately, when COVID-19 finally becomes yesterday’s news, there will probably still be cancer.
While the outlook for people with cancer has vastly improved in the last 50 years, and many cancers have effective treatments, there is still a substantial unmet pharmacological need.
McKinsey and Company tell us that oncology therapeutics accounted for US$143 billion in branded pharmaceutical sales in 2019, or 20% of the total global pharmaceutical market.
Predictions are that this market will sustain a 12% compound annual growth rate (CAGR) and that global oncology therapeutics sales are on track to hit $250 billion by 2024.
“Dumb bombs”
Traditional pharmaceuticals consist of ‘blind’ molecules. They’re deployed in our bodies in an undifferentiated way, to treat a condition – but they don’t target that condition alone.
The sometimes-catastrophic side effects of chemotherapy, one of the most established treatments for cancer, are well documented. And even drugs like paracetamol and aspirin, which are popularly regarded as benign and harmless, can have unpleasant side effects in some patients.
“The emphasis of much of the current work in medicine is to improve the effectiveness of drugs and to reduce their side effects,” said Cynata Therapeutics Ltd’s Dr Ross Macdonald, who is investigating the application of stem cell technology in the treatment of people with respiratory failure due to COVID-19.
“To use an analogy, cell-based treatment is akin to a laser-guided bomb versus a bomb that’s dropped from an aircraft. Your typical drug is like a bomb that’s dropped from an aircraft – effective but a bit uncontrollable. It doesn’t hit its target with precision.
“The problem with a ‘dumb bomb’ drug is collateral damage. You want to destroy the dangerous cells and leave the healthy ones intact.”
The power of the cell
Enter the cell – the living drug spearheading what is known as ‘precision medicine’ – which interacts with its target and its environment in real-time.
As living organisms, cells are the building blocks of biotechnology. They’re preprogrammed to know their way around other living organisms and have an intelligence that traditional pharmaceuticals lack.
In recent years, medicine has been able to reveal a deep understanding of how the many different cells in our immune system interact with one another to produce a coordinated response to infections or injury.
“Science can now harness those activities very precisely in a medical response to an infection or a disease," said Macdonald.
One of the emerging areas of immunology is adoptive cell transfer (ACT), which takes patients’ own immune cells out of their bodies, programs them and reintroduces them into the patient to fight disease.
Letting the patient’s body do its stuff
The growing body of evidence from clinical trials of chimeric antigen receptor (CAR)-T cell therapy gives insight into how the immune system can be harnessed to make much more effective, targeted medicines.
These are T-cells that perform a surveillance function in the body, policing irregular looking proteins in the body – basically anything that shouldn’t be there. As part of the body’s natural immune system, they can eliminate malignancies before they become a problem.
Researchers can now obtain these cells from the patient, medicinise them and deploy them against cancer – and it’s proving to be safe and highly effective.
This next-generation therapy makes significant advances on the traditional raft of cancer remedies – surgery, chemotherapy and radiation therapy, though it can complement these treatments.
"Our recognition of how to harness the power of CAR-T cells has been a huge medical breakthrough,” said Macdonald. “This is one way we have been able to use cells as medical treatment.
“These immune cells are turbo-charged to recognise the specific cancer in that patient and then put back into the patient’s body to do their stuff," says Macdonald. “And patients who previously had very little hope are suddenly in remission and potentially cured with this treatment."
At present CAR-T cell therapy is most effective in blood cancers, but the race is on to employ it in the fight against solid tumours, with clinical trials underway.
Two out of three ain’t bad
“What the medical community and the pharmaceutical industry is trying to do is to develop better medicines,” said Macdonald. “More effective, with fewer side effects – and cheaper in the long run."
So what’s the hold-up? Companies working in this space are confident of meeting two out of the three conditions – safety and efficacy – but a third factor, cost-effectiveness, is still needed to bring a clinical solution to the market.
CAR-T therapies are bespoke and must be manufactured to order. They are therefore prohibitively expensive.
Research investment is being channelled into the ability to manufacture CAR-T therapies at low-cost and at scale, and many believe CAR-T cell therapy is about to reach a tipping point.
Given the unimpeded growth of the global need for safe and effective cancer treatments, and a renewed focus on immunology and immuno-oncology, CAR-T cell innovations seem to be about to meet their moment as a central weapon in the cancer-fighting arsenal in the next decade.