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Journalism of Courage
Remember the mRNA vaccines that were rolled out for the first time during the pandemic? Researchers from Memorial Sloan Kettering Cancer Centre had begun working with the same technology much before to develop personalised vaccines against pancreatic cancer. Their phase I trial, which was recently published in the journal Nature, shows that eight of the 16 patients who received the vaccine were able to mount an immune response against cancer cells. No cancer was detected during the18-month follow-up in these patients. But the cancer came back in approximately13 months after surgery in those among whom the vaccine did not work.
This is an exciting find for oncologists dealing with pancreatic cancer, including Dr Shailesh Shrikhande, who heads India’s highest volume centre for pancreatic cancer surgery at Mumbai’s Tata Memorial Hospital. “This is one of the most difficult solid tumour cancers to treat and the progress in treatments has been slow. It is not for the want of trying, though. The molecular landscape of pancreatic cancer is very diverse. What this means is this kind of cancer has many tumour-promoting pathways that can overwhelm the tumour-suppressing pathways. So even if a therapy targets say four of these pathways, there are many more ways the tumour can continue to grow,” he explains. He remains cautious though. “This is just a phase 1 study, so it is not like I can start providing it tomorrow. There is a long way to go. Even after trials are completed and the therapy becomes available, it has to be accessible and affordable for patients to benefit from it.”
So how does the vaccine work? Unlike an HPV vaccine that can prevent cervical cancer, this vaccine is given to patients with pancreatic cancer after their tumour has been surgically removed and they have had chemotherapy. Pancreatic cancer surgeon Vinod Balachandran and his team from Memorial Sloan Kettering (MSK) came up with the idea for a vaccine when they chanced upon a small group of patients who beat the odds and survived. When they looked at their tumours, they found a lot of immune cells, including T cells on it. This meant that something was signalling the immune system to attack the cancerous cells. The researchers found that in patients who survived, proteins called neoantigens tipped off the T cells, alerting them to the presence of the “foreign” cancer cells. What was more surprising was that even when the tumour was surgically removed, the T cells could keep recognising these neoantigens for up to 12 years. This is similar to how vaccines can elicit an immune response against a pathogen that can last for years, sometimes life-long.
At the same time, researchers from across the ocean were working on mRNA technology that was suited for developing individualised vaccine for cancer. The MSK researchers collaborated with Roche group’s biotechnology company Genentech and the company that developed the Covid-19 vaccine with PfizerBioNTech.To make the individualised vaccine, their tumour was removed in the US and sent to Germany for genetic sequencing. In the lab, tumour mutations that can best produce the neoantigens were selected and mRNA specific to these were manufactured. The mRNA are messengers that carry genetic information to produce these neoantigens to the cells. This then trains the immune system to recognise and fight off the cancer cells. The team continued this back and forth between the US and Germany even through the pandemic.
Says Dr Shrikhande, “In patients with pancreatic cancer, even after high quality surgery – the pancreas are deeply seated making the surgery complex – and a full course of chemotherapy, only about 50 per cent survive.This is because the enemy might not be visible on scans but it is still there.If the vaccine is given after surgery and chemotherapy, it will take over the fight and prevent the cancer from coming back.”
The next step for the team will be to conduct larger randomised control trials and figure out why the vaccine worked in some and not in others. “We will continue to analyse data from the pancreatic cancer trial so we can better understand what factors help the vaccine work in patients. Of course, we want to find out why some pancreatic cancer patients didn’t respond to the vaccine and find solutions to this problem,” said a statement from MSK.
