2023-06-29 11:55:00
There are few effective treatment options for pancreatic cancer, so each new advance in therapy is comparable to a revolution. Researchers in the US treated 16 patients with pancreatic cancer with a personalized mRNA vaccine after tumor removal. In half of the patients, the tumors did not return after a year and a half. Scientists consider this a success in the fight against cancer, which usually returns within a few months after surgery.
Niels Halama, an oncoimmunologist at the German Cancer Research Center in Heidelberg, describes the news as fantastic and speaks of a decisive breakthrough with a completely new approach from Ulm-based gastroenterologist Thomas Seufferlein and his colleague Alexander Kleger.
At the same time, scientists agree that euphoria is premature: more data is needed, because so far there are more questions than answers.
A study published in May 2023 in the journal Nature, based on the results of vaccination of a total of 16 patients. However, this is the first evidence of the successful use of mRNA technology to treat cancer, which is extremely deadly and difficult to treat. It is also a breakthrough in a multi-year effort to develop customized cancer vaccines tailored to the tumors of individual patients.
How the study was conducted
Specialists at the Memorial Sloan Kettering Cancer Center in New York removed the tumor from the patient and sent the material to Germany to the biotechnology company BioNTech, where he was examined for the presence of mutations, the so-called tumor antigens, or neoantigens.
Pancreatic cancer cells Photo: Science Photo Library/IMAGO
Then, neoantigens to be attacked were individually selected for each patient, and an mRNA-based vaccine was produced. It’s called BNT122. Like an mRNA vaccine against the coronavirus, it should elicit an immune response against new cancers in the human body.
This vaccine was administered to patients nine weeks after the operations. The patients also received chemotherapy and so-called checkpoint inhibitors: molecules that prevent cancer from turning off the immune system.
In eight vaccinated patients, there was no immune response – tumors returned to them. The remaining eight patients had an immune response – no new tumors were found in them by the end of the follow-up period. “I’m thrilled that there is a link between immune response and higher chances of survival,” said Nina Bhardwaj, who studies cancer vaccines at Mount Sinai Medical Center’s (MSSM) Icahn School of Medicine. But at the same time he agrees: “Of course, this should be confirmed in larger studies.”
Why is pancreatic cancer so deadly?
The pancreas is a small, pudding-like organ located deep in the abdomen. Problem: Her degeneration is usually late recognized. There are no methods for its early detection yet. Patients show symptoms later. By this time, cancerous tumors have already reached large sizes – several centimeters, and quickly spread to other organs, such as the liver. And even if the tumor can be removed, it often comes back.
Therapy is complicated by the fact that this type of cancer is subject to constant mutations. He changes his environment and changes himself under its influence. This makes it even more difficult to treat.
“In fact, each pancreatic carcinoma is a separate disease,” says Alexander Kleger. This makes it “an example of a tumor for which we want to create a customized therapy, because if it works for one patient, it may well work for others,” adds his colleague Thomas Seuferlein.
Vaccination against pancreatic cancer
The idea of using a vaccine to fight cancer is not new. In 2010, a prostate cancer vaccine was approved in the United States. There has also been research into mRNA vaccines against this type of cancer for some time. Only recently, an mRNA vaccine developed by Moderna and Merck has shown success in the treatment of malignant melanomas.
However, many scientists did not expect that vaccination could help with pancreatic cancer. Pancreatic cancer is known as a so-called “cold tumor”, which does not elicit a strong immune response and therefore hides better from the immune system. “Cold tumors” usually do not respond to immunotherapy. “I know that researchers have studied a number of different types of cancer and I’m surprised it worked so well for the pancreas,” says immunologist Drew Weissman of the University of Pennsylvania.
Optimism and many questions
However, despite all the euphoria, caution must be exercised. First, the study is small. Secondly, the observation period is short. In addition, the study was conducted without a control group, that is, without a comparison group in which patients were operated on, received chemotherapy and were not vaccinated. Thus, the effect of vaccination is difficult to measure and it is not possible to compare it with previous treatments. What further limits comparability is the fact that each patient received an individual, tailor-made vaccine.
It is not yet clear why vaccination resulted in an immune response in only half of the patients. And also: is it possible and how to improve the selection of neoantigens in the future. Interestingly, the mRNA vaccine against coronavirus, introduced during the same period, led to an immune response in the vast majority of patients.
Pancreas Photo: Ersin Arslan/Zoonar/picture alliance
It is also not clear whether vaccination also helps those patients whose tumors are so advanced that they cannot be operated on. During the study, only patients whose tumors had been removed received the vaccine.
“At a more advanced stage, I think the situation may be different,” said Nina Bhardwaj. There are many factors that suppress the immune system. Pancreatic cancer is characterized by a large tumor. “Even if a good immune response can be elicited, it will not be easy to introduce the necessary T cells into the tumor itself.”
Based on the above arguments, vaccination cannot be taken as a panacea as the only effective treatment option. However, according to experts, it is quite possible that it can be used as a support, for example, at the metastatic stage of the disease.
Cancer vaccines are very expensive
At the moment, very practical questions arise: how much can be accelerated in the production of pancreatic vaccines? How expensive will vaccination be once it is available to all patients in need? BioNTech founder Ugur Şahin told the New York Times that over the past few years, production has been reduced to six weeks and production costs have dropped from $350,000 to $100,000 per dose. “And with a clinical application of this magnitude, we can assume that there will be additional opportunities to reduce the price as the process progresses,” said Nils Halama, an oncoimmunologist.
Could mRNA vaccines revolutionize cancer treatment?
The vaccine production process, which experts call very complicated, can only be organized in specialized centers. “Now there are probably two or three centers in the world that can produce such a vaccine. After all, we need a vaccine that can be used anywhere in the world,” emphasizes Drew Weissman.
Experts believe that scientists and practitioners have a lot of work to do. It’s time to put vaccination into practice, says mRNA researcher immunologist Weissman. He is convinced that not all types of cancer will respond to a new type of vaccine. So maybe it’s not a revolution yet, but it’s an important step in cancer therapy, especially pancreatic cancer.
See also:
#mRNA #vaccine #save #deadliest #cancer