Space age genetic engineering offers hope for pancreatic cancer

Lynne Walker, Chair of the Board of Trustees of the charity Pancreatic Cancer UK, knows that she is very lucky indeed: she is alive.

Pancreatic cancer affects nearly 10,000 people a year in the UK, and five years later, only 7 per cent of these patients are still living. This compares with 80 per cent survival rates for breast cancers and other formerly highly lethal diseases. There has been virtually no improvement in the survivability of this kind of disease in 40 years.

Like most afflicted by this terrible type of cancer, Lynne was diagnosed almost by accident, in 2009 after she returned from a long-distance business trip complaining of exhaustion and a bad back.

She’d been pestering her GP for months and she had been investigated for a possible gall bladder complaint, but she was told there was nothing wrong. “I was running a successful management consultancy and I didn’t pay much attention to my aches and pains,” she reflects.

Lynne

Then, soon after she got back from Australia, feeling more than usually jet-lagged, she got up one morning to find she had turned completely yellow: it was an acute case of jaundice, in combination with the other symptoms, a clue as to what was really going on.

“This looks very serious,” her GP said, “I think we should call an ambulance.”

The penny had dropped at last and a specialist told her that she had a 50/50 chance of making it. She spent six months in hospital, during which she suffered sepsis, multiple organ failure and artery collapse, and nearly died several times.

She emerged, very much alive but as she says with a twinkle in her eye, “organ light,” the surgeons having saved her by chopping out half the diseased pancreas her gall bladder and duodenum and re-plumbed the rest– an option available only in a very few cases.

Often too late for surgery

The disease is especially hard to diagnose in part because of where the pancreas is located, deep within the body. It is hidden away behind the stomach and in front of the spine. Its function is to produce insulin, and other juices that help with digestion.

Location alone means that the disease is almost always advanced when it is first spotted, usually by accident as in Lynne’s case. It is especially nasty because it starts to metastasise, or replicate itself uncontrollably, before the tumour is big enough to be spotted on a CT or PET scan.

It is often too late for surgery. Conventional chemo and small-molecule targeted therapies are not effective, and the search is on to find a more reliable way of treating this most intractable of diseases.

Prof Nick Lemoine, the distinguished cancer research scientist who is director of the Barts Cancer Institute, is leading a three year research project to find a treatment using state of the art immunotherapy.

As explained in an earlier post, this means helping the body’s immune system to knock out the cancer cells, rather than seeking to poison cancer cells with the blunderbuss of chemotherapy.

Lemoine, who has a colourful turn of phrase as well as the most profound understanding of molecular biology, asks whether I have ever eaten sweetbread, that tasty morsel occasionally served up as a side-dish to a Sunday roast.

Prof Lemoine

A healthy pancreas is squashy like a lightly grilled sweetbread, explains Prof Lemoine, but a cancerous one is hard and gritty. Somewhat graphically, he explains that when you cut one with a scalpel, it feels like cutting an unripe pear. “You can hear the crunch as you go through…”

That hardness is due to fibrous tissue — a kind of Kevlar vest which neither chemo, nor the immune system’s killer T cells, have been able to penetrate effectively. It’s simply impossible to get in.

Cutting edge technology in virology and immunology

The solution is space age genetic engineering, drawing on cutting edge technology in virology and immunology.

The first step is to identify and build the kind of T Cells that will bind naturally to the antigens, the markers on the surface of the cancer cells. These specially engineered cells are called Chimeric Antigen Receptor (modified T) or CAR-T cells. They are brewed up in the lab using the patient’s own cells, then re-injected into her bloodstream.

The treatment will also deploy a class of viruses that target tumours. Astonishingly, research led by Prof John Marshall at Barts shows that part of the foot and mouth virus is exquisitely effective in seeking out and destroying cancer cells – the kind of serendipitous discovery that can lead to breakthrough medicine.

The virus creates a powerful danger signal that stimulates the immune system.

The third element of the therapy is to use known agents to pipe this cocktail of agents into the tumour by opening up the blood vessels that feed into the pancreas.

As Lemoine puts it, the overall effect will be to create a “weaponised T Cell” that punches through the Kevlar shield and goes to work on the cancer cells. “They will have nowhere to hide,” he says, looking like a medical version of Clint Eastwood tracking down an especially malevolent villain.

If this sounds futuristic, it is: the study alone will take three years and the resulting therapy will be exceedingly expensive and a long way from being generally available to patients. The objective is to get a treatment ready for clinical trial where its impact on patients can be properly evaluated before taking a drug to market.

But it is the start of a systematic and scientific attempt to treat a disease that has long gone ignored. Relatively low incidence and high mortality has made it unattractive for drug companies to invest in finding a cure, and sadly few people have survived long enough to become the kind of high profile, celebrity ambassadors that breast and prostate cancer have attracted.

At last, the disease is being given the attention it deserves.

To give the last word to Lynne, one of the rare survivors:

“I owe my life to the excellent treatment I received on the NHS. Yes, I had a positive mental attitude throughout, but I am aware that luck played a very large part in my survival.

“It cannot be acceptable in this day and age that for a disease like this we have to rely on luck. We need early diagnosis and we need treatment options.”

Prof Lemoine’s pioneering project is showing the way.

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