Has cancer finally met its match?

Jamie Morton goes inside the immunotherapy revolution.

Let’s not mince words: it’s a barn-storming, breathless revolution.” Professor Graham Le Gros doesn’t mean to come off sounding over the top. It’s just he’s palpably excited about the promise of an area of medical research we hear too little about.

Think of being able to beat cancer, with little else but our own immune system. Think of a world where we and our loved ones don’t have to suffer through the pain of surgery or chemotherapy.

Think of our bodies, charged up by some of the smartest drugs ever designed, raising an army of billions of cells trained to kill every trace of cancer that emerges within us, before it can gain a foothold.

Le Gros, a world-renowned immunologist, is talking about immune therapy stimulants.

From his office in a distinctive circular brick building overlooking Wellington Harbour high in the hills of Kelburn, Le Gros has been witnessing the first waves of a revolution.

He directs the Malaghan Institute of Medical Research, a small operation that has been playing a disproportionately large role in the global landscape of cancer immunotherapy.

Named in 2013 as the breakthrough of the year by Science magazine, cancer immunotherapy has gained a profile with a new generation of drugs we call checkpoint inhibitors.

One of these was this month funded in New Zealand for the first time to use against the most common form of lung cancer. Its name is Pembrolizumab. We know it better as Keytruda. A wonder drug that tens of thousands of Kiwis successfully pushed to get on to Pharmac’s schedule, Keytruda seems to encapsulate our idea of the latest and greatest weapon in the war against our biggest killer.

But Le Gros says it is now time people heard about the other side of the immunotherapy story. Because, over the next decade, it’s inevitable they will anyway.

Malaghan’s research looks at different ways to stimulate powerful responses against cancer cells, through better understanding the way the immune system “programmes” certain cells to attack tumours.Its scientists do this by using cellular vaccines — taking a patient’s own immune cells and “educating” them to recognise cancer cells — or by novel chemical compounds that achieve similar results.

They start by looking at basic immune cell interactions to design therapies they can trial in humans. Chief among them are antigenpresenting “Dendritic” cells, which Le Gros likens to the gatekeeper, even the emperor, of the immune system.

Breakthroughs in understanding these vital pieces of our biological armour have come in tandem with explosive leaps in big data, bio-informatics, and molecular and cellular biology. Yet you could argue cancer immunotherapy has been around since Queen Victoria was still on the throne.

In the 1890s, a New York bone surgeon named William Coley created a concoction of killed bacteria that he claimed could treat cancer.

Coley’s toxins, which brought on a hellishly high temperature, have been recreated in modern versions still available in some countries, despite no available scientific evidence to support claims the agent can treat or prevent cancer.

“Basically, you just lie on the floor, shiver and shake, and feel like you’ve had 10 doses of the flu,” Le Gros says with a laugh. “If it doesn’t kill you, then the cancer eventually will.”

Approaches that tried to target the immune system gave way to other treatments, notably radiation therapy and chemotherapy, which rose to prominence over the last century.

At that time, it was not surprising that scientists, whose understanding was limited to the brain or endocrine hormones like those found in diabetes, had no clue of the enormity and power of an immune system and its ability to keep us alive for the better part of a century.

They could not imagine what they were really dealing with was a tissue, packed full of loose cells that interrogated every inch of our body, every second of the day.

But there were flashes of insight. Le Gros recalls when he was a young man at the start of his career, seeing Kiwi DNA pioneer Jim Watson’s excitement at how cytokines, a category of small proteins important in cell signalling, might be the key to curing cancer.

“We all watched breathlessly, and nothing happened.”

Nevertheless, Watson was on the right track. His vision was to create long-term cell lines involving T cells, a sub-type of white blood cells that much of today’s immunotherapy efforts revolve around.

They’re of crucial importance because they can fight cancer at the same intricate, individualised level at which cancer attacks us.

After all, cancer isn’t just one disease, and even similar tumours can act differently depending on our genetic make-up and immune system.

To understand cancer is to understand our bodies are made up of trillions of cells, all of which renew in a controlled way that keeps us healthy.

When this control is lost — either through a cellular abnormality such as a genetic mutation, or exposure to a carcinogen, such as those within tobacco smoke — cells begin to multiply unchecked instead of just renewing themselves.

Once there are enough to form a group, a tumour or growth is created, and too many of us learn about when it’s too late. Today, and every other day, 60 Kiwis learn they have some form of cancer.

Among the leading causes of death of New Zealanders is one of the most common, breast cancer, and one of the hardest to treat, lung cancer.

But against these complex and highly variable cancers, we can deploy T cells. An essential part of our immune system, they roam around our bodies and are normally primed to eliminate cancer cells.

Through the view of an electron micrograph, these roving sentries appear as cute little balls of fuzz, rather than the ruthlessly efficient virus killers they are.

Cancer cells, diabolical as they are, out-fox them.

They use certain enzymes to block the body’s immune response by binding to and turning off the T cells, while also switching on a safety mechanism called the checkpoint system, which holds the T cells back.

Keytruda works through a compound that inhibits the ability of cancer cells to block the immune system, and releases the brakes on T cells to unleash them upon the tumour.

In trials, Keytruda has been shown to be twice as effective as chemotherapy, halting, even shrinking tumour growth for 34 per cent of patients with advanced malignant melanomas. The draw-back to checkpoint inhibitors is the immune cells will also attack healthy tissue and cause serious autoimmune disease.

If these agents were the ambulance at the bottom of the cliff, the stimulants Le Gros and his colleagues are exploring is the one at the top.

“We have realised we’ve learned enough about the immune system, and it’s not just about making B cells, or lots of antibodies: it’s about making the T cells very specific and very targeted towards the mutations in the cancer cells.”

Their approach is to build and programme a large army of T cells specifically targeted to go after a