Nine out of ten people do not survive pancreatic cancer, and the survival rate has not improved for almost 60 years. There are almost no effective treatment options. That’s why every advance in therapy is a revolution. And that’s exactly what happened today.
US researchers treated 16 pancreatic cancer patients with a personalized mRNA vaccine after their tumors were surgically removed. At the end of the 18-month trial period, half of the patients did not return. For cancer that usually returns within a few months after surgery, that is a great achievement.
In the world of medical science, superlatives few and far between. In this case, however, pancreatic cancer experts are more than a little excited: Niels Halama, a tumor immunologist at the German Cancer Research Center in Heidelberg, describes the latest -progress as “wonderful” and “unexpected” news. Thomas Seufferlein, a gastroenterologist from Ulm, declared that this was a decisive breakthrough in a “completely new approach”. His colleague Alexander Kleger called it a “huge step” that would revolutionize the field.
With Only 16 patients, the study, published in the journal Nature, very little. However, it provides the first evidence of the successful use of mRNA technology for one of the deadliest and most difficult to treat forms of cancer. It’s also a decisive breakthrough in years of efforts to develop cancer vaccines that are tailored to individual patients’ tumors.
What was done during the study?
on the Memorial Sloan Kettering Cancer Center in New York, the tumors were removed from the patients and sent to Germany. The genome of the tumor tissue is then sequenced by the biotechnology company BioNTech and checked for mutations, called neoantigens.
A selection of previously targeted neoantigens compiled individually for each patient – itself a very complex process based on years of research – and an mRNA-based vaccine was created. As with the mRNA vaccine against COVID-19, the purpose is to stimulate an immune reaction against these neoantigen structures.
This vaccine is given for the first time nine weeks later the patients underwent surgery to remove the primary tumor of the pancreas. In addition, patients also receive chemotherapy and so-called checkpoint inhibitors (these are molecules that prevent the cancer from shutting down the immune system).
In the eight patients who showed an immune response, the tumor did not return at the end of the study. The other eight patients did not show an immune response – they relapsed.
“I am very pleased with the fact that there is an apparent correlation between the induction of immunity and the early signs of longer-term survival,” said Nina Bhardwaj, who researches cancer immunology at the Icahn School of Medicine in New York at Mount Sinai, added. whose findings need to be confirmed in larger clinical trials.
Why Is pancreatic cancer fatal?
The pancreas is a small organ located deep in the abdominal cavity. Carcinoma is one of the leading causes of cancer deaths worldwide. The main problem is that pancreatic cancer is usually found at a late stage. There is no early detection method, and patients usually have no symptoms until the cancer becomes unusually large or has spread to other organs. Although it is possible to remove the tumor through surgery, it often returns.
Another factor that complicates therapy is that cancer is always changing. It changes its environment and changes itself in its environment. As a result, no two pancreatic cancers are the same. This makes it especially difficult to treat.
“Each Pancreatic cancer is like a disease in its own right, “said Alexander Kleger. That makes it a “prime example of a tumor where you want to create an individual therapy,” explains Thomas Seufferlein.
Scientists surprised by the effectiveness of the vaccine
the The idea of fighting cancer with the help of a vaccine is not new. A vaccine against prostate cancer has been approved in the US. back in 2010. And research on mRNA vaccines for cancer has also been going on for a long time. Recently, an mRNA vaccine developed by the companies Moderna and Merck has shown success in treating high-risk melanoma.
However, many scientists do not expect a vaccine against pancreatic cancer to work. Pancreatic cancer, after all, is categorized as a “cold tumor,” meaning it doesn’t elicit a strong immune response and thus hides better from the immune system. Cold tumors usually do not respond to immunotherapy.
“I know they’re looking at a bunch of different types of cancer,” said Drew Weissmann, an immunologist at the University of Pennsylvania. “I was surprised that the pancreatic one worked so well.”
Watchful optimism – and many unanswered questions
However for all the initial excitement, some measure of caution is also necessary. With only 16 patients, the study was as small as the 18-month observation period was short. It was also conducted without a control group, meaning there was no comparison group that only received surgery, chemotherapy and checkpoint inhibitors. The effect of vaccination alone is difficult to measure, and comparison with previous therapeutic methods is also difficult. The fact that each patient received an adapted vaccine also made it difficult to make a comparative analysis of the study results.
it it is not yet clear why the vaccination resulted in an immune response against cancer in only half of the patients, or if and how the selection of neoantigens could be optimized in the future. Interestingly, an mRNA vaccine against COVID-19 given at the same time led to an immune response in all patients, indicating that their reaction to neoantigens was not impaired in any way.
It’s also unclear whether the vaccine can help patients whose tumors are so advanced that it can’t be effectively used. The study included only patients who could have their tumors removed.
“In advanced disease, I think the situation different,” says Nina Bhardwaj. “Maybe there are more immune suppressive factors at play. And even if you can generate a good immune response, getting the right cells – in this case T cells – into the tumor itself can be difficult. a great big tumor.”
For this reason, vaccination alone may prove to be an inadequate treatment. However, experts emphasize that it can be considered to use it as a supplementary therapy, for example in the metastatic stage.
It can be mRNA Are vaccines changing cancer treatment?
At this stage, there are also many practical questions: How much to speed up the process? How expensive is a vaccine once developed? BioNTech founder Ugur Sahin told the New York Times that over the past few years, the company has been able to reduce production times to less than six weeks, and reduce production costs from $350,000 to at $100,000 per treatment. “And with a clinical application on this scale, we can imagine that there are many opportunities to reduce the price further down the road,” said tumor immunologist Niels Halama.
It is also questionable if the process, described by experts as very complex, can be established outside of special centers. “This is a vaccine that now probably needs two or three centers in the world to make it,” said Drew Weissman. “But in the end, we want a vaccine that is available worldwide.”
Much work remains to be done, and many unanswered questions remain. For now, trial and error is the order of the day, according to Drew Weissman. He is convinced that not all cancers will respond to an RNA vaccine. So maybe it’s not a revolution yet. But it could prove to be an important next step in improving how we currently treat pancreatic cancer.
