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 recently approved for use as a first line treatment in New Zealand 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 antigen-presenting "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 person's cancer cells in its earliest stages.
"Our cancer immunotherapy team, led by Professor Ian Hermans, has discovered that a group of immune cells, called NKT cells, are very good at training cancer-killing T cells, and they are vigorously testing the safest ways to fire up the NKT cell activity and get them working against cancer."
We could think of the NKT cells as drill sergeants in a boot camp, Le Gros says, instructing soldier T cells to seek out and destroy their specific enemy.
But how to teach them what to hunt for?
The bio-informatics revolution and advances in computing power have taken scientists to the point where sequencing technology can now, quite cheaply, churn through 10 million cells and pick out the one or two mutations responsible for causing the cancer.
"And what's amazing is that now, with the turn-around time of a month, we can use chemistry to synthesise those mutations.
"So we're talking about a situation where, okay, here's your cancer, whip it out. Now let's sequence it, okay, so this is what it is. Now, let's turn it into a protein, and then into a vaccine that can be used to prime up the T cells."
The obvious barrier is the personalised nature of cancer. "If we were all like identical twins, we could create immune-stimulating products to buy straight off the shelf, but because every individual on the planet has their own unique set of immune response genes, we have to tailor-make immune therapies to fit with an individual's immune markers."
As such, the more generally targeted checkpoint inhibitors are much further down the track in clinical development than the highly individualised immune therapy stimulant.
Even so, scientists have an untapped arsenal of different cell types and sub-types in our immune system that could be manipulated for cancer therapy.
"I think we are going to have some remarkable breakthroughs in the next 5-10 years, as immunology has never had the investment it's getting now.
"What's happened with Keytruda is funders have realised: hey, this stuff works. And we've never had the real power of the pharmaceutical industry behind immunology.
"I do get stressed because there is so much good stuff going on and I'm just thinking, how can we stay part of it in little old New Zealand?"
As it happens, Kiwi researchers are in a great position to make waves. Only last month, the Malaghan Institute announced a multi-million dollar partnership with China-based Hunan Zhaotai Medical Group to push for developments in an area of oncology known as CAR-T cell immunotherapy.
In this transfusion-like therapy, some of the patient's own T cells are modified to express a specific receptor - a chimeric antigen receptor (CAR) - in order to redirect them against cancer cells.
The cells are then administered to the patient to target the tumour.
"The CAR-T cell technology is a major breakthrough, because they are genetically created T cells, and when they are programmed, they don't stop," Le Gros says. "They're remorseless in the way they chase the cancer around the body until it's all gone."
Malaghan's Chinese collaborators already had a pipeline of therapies that had undergone initial clinical trials in China, which were now ready to be developed under a Western regulatory environment here.
Chemists at the Victoria University-based Ferrier Research Institute are meanwhile developing a synthetic cancer vaccine technology that can activate tumour-specific T cells, producing a targeted immune response.
This synthetic cancer vaccine had already shown a rejection of cancer in several types of animal models.
Le Gros expects to see further big cancer gains in the coming years from Hermans' cutting-edge research programme, which delved into how innate immunity could be used to supercharge adaptive immunity against cancer.
"Ian has that rare insight into how this part of the immune system really ticks - it comes from many years of research, trial and failure, and it's exciting to watch."
Professor Kath McPherson, chief executive of the Health Research Council of New Zealand, is just as excited.
"Research in these areas is advancing knowledge, and practice, in ways we probably couldn't have dreamed about a few years ago," says McPherson, whose organisation has invested millions of dollars in Malaghan and other cancer immunology studies.
"There is a sense of optimism about this field within science, a sense that this might well be the way we could, and should, get better outcomes for more people.
"This is definitely a field that holds promise, although we have more to do yet."
Renowned cancer researcher Distinguished Professor Bill Denny, director of the Auckland Cancer Society Research Centre at the University of Auckland, agrees.
He sees immune therapy stimulants as "directly complementary" to check-point inhibitors, but adds the area is looking increasingly attractive to major research funders like the society.
For his part, Le Gros sees no reason why stimulants couldn't one day do the job by themselves. Was this really a possibility?
"Hell, yes," he answers.
"Chemotherapy is bloody awful, and even surgery [isn't a good thing]. It can leave you with scar tissue, or not being able to pass bowel movements
"The key is using the body's own tricks. We've tried putting highly inflammatory stuff in and it doesn't work. We've made mistakes with these blunderbuss approaches.
"You need to be targeted, and you need to let the body do most of the work naturally."
But he acknowledges that, until we are sure stimulants work better than what is currently available, we should be using them alongside conventional treatments.
"We can't treat people as guinea pigs."
Whether it will prove to be stimulants, or something else like gene-editing technology that first seizes the holy grail of defeating cancer, Le Gros can't say.
"However, I do think we are coming to the understanding that cancer need not be ignored as an unconquerable older person's disease, and that it can and should be cured.
"An increasing number of very long, involved experiments are making us realise that we don't have to die of cancer - that it's not inevitable - and I think that's really great.
"It's giving us hope."
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