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Fresh hope on one of toughest cancers to cure

Results from a small study of a pancreatic vaccine are promising enough to merit cautious optimism. Researchers are figuring out how to train immune cells to see and destroy cancers — even devastating ones such as pancreatic cancer.

Any progress against pancreatic cancer should be lauded, but the vaccine still has a lot to prove before reaching the market. And even if it gets there, it can only — for now — help a small slice of pancreatic cancer patients.

No matter its long-term success, though, the study is important for its lessons about how to target pancreatic cancer — and what it says about the potential to use the immune system to battle more types of tumours.

In the study, led by oncologists at Memorial Sloan Kettering who teamed up with BioNTech in Germany, 16 people with pancreatic cancer were given the vaccine alongside chemotherapy. The vaccine prompted an immune response in half of the patients. After 18 months, none of them showed signs of disease recurrence.

That such a small study has generated so much excitement reflects this cancer’s notoriety. While early detection, lifestyle interventions and better treatments have helped people with other cancers live longer, the five-year survival rate for someone with a pancreatic cancer diagnosis is just 12 per cent. By 2030, pancreatic cancer is projected to be the second-leading cause of cancer deaths in the United States, surpassed only by lung cancer.

Because pancreatic cancer tends to be so swift, one big lesson from this study is simply that it is possible to create a vaccine quickly enough to make a difference. Much like Moderna and Merck’s cancer vaccine, which recently generated excitement for its potential to prevent melanoma from returning, these shots are tailored to a patient’s own tumour. Memorial Sloan Kettering researchers sent samples to BioNTech, where the tumour was analysed to determine which mutations might elicit a helpful immune response. The recipe for up to 20 of those proteins were encoded in a personalised mRNA vaccine that was mailed back to the oncologists.

Technology — inexpensive and rapid genome sequencing, AI and mRNA — made it possible for patients to get their first doses in about nine weeks after their surgery.

The trial’s other big lesson is that an mRNA vaccine can elicit an immune response even in people with a cancer with few mutations. Until now, the conventional wisdom with cancer vaccines is that they will work best, and perhaps work only, in tumours with lots of mutations — such as melanoma. That’s because the vaccine trains the immune cells to spot what is different about cancer cells — mutated proteins — so they will mobilise to destroy them.

Yet this vaccine created a robust immune response even though pancreatic cancers have few mutations, says Vinod P. Balachandran, the pancreatic cancer surgeon at Memorial Sloan Kettering Cancer Centre, who led the study. That finding could signal broader applicability of personalised cancer vaccines.

There is an important caveat, though: because a biopsy does not give researchers enough material to analyse, this bespoke vaccine can be created only for patients who are able to undergo surgery to remove their tumours. That’s at most about 20 per cent of the pancreatic cancer population. That’s also the population that has the best chances of responding to a vaccine.

Decades ago, researchers were trying to use therapeutic cancer vaccines in people with advanced disease. At that stage, not only is the cancer a problem, but patients, in particular pancreatic cancer patients, have a host of other health issues that dampen the immune response. Trying to rev up those T-cells in that scenario with a vaccine alone is like trying to roll a boulder uphill, says Anirban Maitra, a pancreatic cancer specialist at MD Anderson in Houston. After surgery, the immune system is going up against a much more manageable enemy.

The Memorial Sloan Kettering researchers demonstrated how well that could work. After vaccination, one patient developed a suspicious lesion in the liver that harboured a mutation found in the pancreatic tumour, suggesting the disease had spread. Tests and images showed vaccine-trained immune cells crowding to the site. Later, the lesion disappeared. “That’s exactly what the vaccine is supposed to do,” Maitra says.

While this vaccine — and others in development — wind through clinical trials, the field should be throwing everything into figuring out how to ensure more patients can benefit from it. That will mean diagnosing pancreatic cancer earlier. Some 80 per cent of pancreatic cancers are discovered after tumours have already spread to other organs, a point where most patients cannot undergo surgery and their chances of surviving the disease are vanishingly small.

But here, too, there is good news. In another promising study last week, researchers used artificial intelligence to analyse the medical records of millions of patients from Denmark and the US, including nearly 28,000 who developed pancreatic cancer. By looking across decades of data, the group identified a cluster of symptoms that could be early signs of cancer nearly a year before it was diagnosed in real life. Ideally, this information could be used by doctors to identify and monitor patients at risk of developing the disease, allowing many to undergo surgery and treatment before tumours have spread.

The caveats to these studies are many. But there is finally real hope that the bleak survival statistics for pancreatic cancer could meaningfully change.

Lisa Jarvis is a Bloomberg Opinion columnist covering biotech, healthcare and the pharmaceutical industry. Previously, she was executive editor of Chemical & Engineering News

Lisa Jarvis is a Bloomberg Opinion columnist covering biotech, healthcare and the pharmaceutical industry. Previously, she was executive editor of Chemical & Engineering News

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Published May 18, 2023 at 8:00 am (Updated May 17, 2023 at 3:01 pm)

Fresh hope on one of toughest cancers to cure

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