Pancreatic cancer vaccine?

US researchers treated 16 pancreatic cancer patients with personalized mRNA vaccine After surgical removal of the tumor. Half of the patients were relapse-free by the end of the 18-month study period. For cancers that usually recur within months after surgery, this is a big win.

In the world of medicine, there are very few superlatives.However, in this case the pancreas cancer Experts are more than a little excited. Niels Harama, a tumor immunologist at the German Cancer Research Center in Heidelberg, called the latest development “great” and “unexpected” news. Ulm’s gastroenterologist Thomas Sefferlein declared this a decisive breakthrough with a “completely new approach”. His colleague Alexander Kreger called it a “big step” to revolutionize the field.

The study, published in Nature, is small, with only 16 patients. However, it provides the first evidence of the successful use of mRNA technology against one of the deadliest and most difficult to treat cancers. It is also a crucial advance in the long-standing effort to develop cancer vaccines tailored to individual patient tumors.

What happened during your research?

At Memorial Sloan Kettering Cancer Center in New York, tumors were removed from patients and sent to Germany. The genome of the tumor tissue was then sequenced by the biotechnology company BioNTech and tested for the presence of mutations, so-called neoantigens.

The selection of targeted neoantigens is then individualized for each patient, itself a highly complex process based on years of research, mRNA-based vaccine was produced.like an mRNA vaccine against COVID-19the goal was to induce an immune response against these neoantigen structures.

The vaccine was first given nine weeks after the patient underwent surgery to remove the primary pancreatic tumor. In addition, the patient received chemotherapy and so-called checkpoint inhibitors (molecules that prevent cancer from shutting down the immune system).

In eight patients who showed an immune reaction, the tumor had not recurred by the end of the study. Her other eight patients showed no immune response and relapsed.

“We are very excited by the fact that there is a clear correlation between the induction of immunity and early signs of long-term survival,” said Nina Bhardwaj, a cancer immunology researcher at the Icahn School of Medicine Mount Sinai in New York. There are,” he added. This finding will need to be confirmed by large clinical trials.

Why is pancreatic cancer so deadly?

The pancreas is a small organ located deep in the abdominal cavity. Cancer is one of the leading causes of cancer death worldwide. The main problem is that pancreatic cancer is usually detected at a very late stage. There is no way to detect it early, and people usually have no symptoms until the cancer is too large or has spread to other organs. Even if the tumor can be surgically removed, it often recurs.

Another factor that complicates treatment is that cancer is constantly changing. It modifies its environment and itself is modified by that environment. As a result, no two pancreatic cancers are the same. This makes treatment particularly difficult.

“Any pancreatic cancer is a disease in itself,” says Alexander Kröger. As such, this would be “a prime example of a tumor where we want to create personalized treatments,” explained Thomas Severlein.

Scientists marvel at vaccine effectiveness

The idea of ​​fighting cancer with the help of vaccines is not new. A vaccine against prostate cancer has been approved in the United States. And research into mRNA vaccines against cancer has also been done for some time. Most recently, an mRNA vaccine developed by Moderna and Merck was shown to successfully treat high-risk melanoma.

Still, many scientists didn’t expect a vaccine against pancreatic cancer to work. After all, pancreatic cancer is classified as a “cold tumor,” which means it hides well from the immune system because it does not provoke a strong immune response. Cold tumors usually do not respond to immunotherapy.

“I know they were looking at different types of cancer,” says University of Pennsylvania immunologist Drew Wiseman. “It’s amazing that the pancreas was such a well-functioning organ.”

Cautious Optimism — and Many Unanswered Questions

It’s exciting at first, but it also requires some caution. The study was small because he had only 16 patients and the short 18-month follow-up period. Also, this study was conducted without a control group, ie, a comparison group that received only surgery, chemotherapy, and checkpoint inhibitors. Therefore, it is difficult to measure the efficacy of vaccines alone and to compare them with previous treatments. The fact that each patient received a custom-made vaccine also makes comparative evaluation of study results difficult.

It is still unclear why vaccination elicited an immune response against cancer in only half of patients, or whether and how neoantigen selection can be optimized in the future. Interestingly, an mRNA vaccine against COVID-19 given over the same period elicited an immune response in all patients, indicating that the response to neoantigens was somehow intact.

It is also unclear whether vaccination will help patients whose tumors are already advanced and virtually inoperable. This study included only patients whose tumors could be resected.

“In advanced disease, I think the situation is different,” says Nina Bhardwaj. “There are probably a lot of immunosuppressive factors already at work. And even if you generate a good immune response, it can be difficult to get the right cells (T cells in this case) into the tumor itself. It’s a big, bulky tumor.”

For this reason, vaccination alone may not be an adequate treatment. However, experts stress that it could potentially be used as an adjuvant therapy, such as in the metastatic stage.

Will mRNA vaccines revolutionize cancer treatment?

There are also many practical questions at this stage. How far can the process be accelerated? How much will it cost once a vaccine is established? He said he was able to cut it to less than a week and reduce the production cost per treatment from $350,000 to $100,000. “At clinical applications of this magnitude, we can envision further price reductions and more opportunities in the future,” said immuno-oncologist Niels Jarama.

It is also questionable whether this process, which experts describe as very complex, can be established outside specialized centers. “This is a vaccine that probably needs two or three vaccine development centers in the world right now,” said Drew Wiseman. “But ultimately we will need a vaccine that can be used worldwide.”

Much remains to be done and many open questions remain. Drew Wiseman says trial and error is the norm for now. He is convinced that not all cancers respond to his RNA vaccine. So maybe this is not yet a revolution. But it could be an important next step in overhauling current pancreatic cancer treatments.