Of the more than 100 known types of cancer, pancreatic cancer is the deadliest. 88% of patients die despite having received the available treatments, mainly surgery and chemotherapy. This terrible statistic has a bright reverse: 12% of patients survive. Some live for years, even more than a decade, without relapse. In medical terms they are cured. How do they get it?
That question has inspired the development of an RNA-based pancreatic cancer vaccine, the same molecule that allowed immunizations against covid to be created in record time. The results of the first tests on patients—just 16 people in a first batch of trials—have just shown promising results. The vaccine has managed to activate the immune system of half of the patients. None of them had a relapse in the time the trial lasted: 18 months. On the other hand, all the patients in whom the vaccine did not cause a reaction suffered relapses.
The results are still very preliminary, but they mark an important milestone in a field in which treatments and patient survival are barely they have improved in the last 40 years.
Pancreatic cancer is the tumor cold quintessentially. In oncology jargon, this means that the immune system is unable to detect it and trigger inflammation—heat—to kill it. That is why immunotherapy does not work in the pancreas, cancer treatment most successful in recent years. What is surprising is that the tumors of long-term survivors are ablaze: in them there are up to 12 times more immune cells than in other patients. Those immune cells are killer T lymphocytes, a type of white blood cell capable of killing other cells. The T cells of the survivors have learned to identify the aberrant proteins that the tumor produces—called neoantigens— and annihilate it.
“After analyzing samples from long-term survivors, we wondered if we could emulate it in the rest of the patients,” Vinod Balachandran, a doctor at the Sloan Kettering Cancer Center in New York and leader of the team that has developed the vaccine, explains to this newspaper. The most important thing, he believes, is that contrary to what was thought until now, pancreatic cancer does produce molecules that allow the immune system to launch against it.
The results are published this wednesday in the magazine Nature, reference of the best world science. Together with Balachandran, they sign Ugur Sahin and Özlem Türeci, the already famous couple of Turkish origin who founded BioNTech and created the successful covid RNA vaccine in collaboration with Pfizer. The truth is that both set up their company precisely with the idea of getting the first effective vaccines against cancer.
In this complex clinical trial, it was necessary to manufacture a vaccine for each patient. After removing the tumors from the abdomen of the 16 participants, the researchers sequenced their genome and identified up to 20 neoantigens. Then they created RNA vaccines that contained the recipe for each one to synthesize the specific molecules of his tumor in his body.
At this point they were given atezolizumab, an immunotherapy drug, a dose of vaccine, and finally mFolfirinox, a type of chemotherapy. Then they gave a booster dose. In addition to the positive results in 50% of the aforementioned patients, the researchers observed that the number of killer lymphocytes increased in their body, which is probably behind the absence of relapses. Balachandran explains that they hope to start “soon”, together with BioNTech, the second phase of more detailed tests and with more patients, something essential to clarify the real effectiveness of the vaccine.
An 18-month survival without relapse is a very respectable time.”
Ignacio Melero, University of Navarra Clinic
“These results are very promising and set the stage for a second phase of clinical trials,” highlight Amanda Huff and Neeha Zaidi, researchers at Johns Hopkins University (USA) who were not involved in the study, in a comment Also posted this Wednesday. These cancer vaccine specialists highlight a startling observation. One of the patients who responded to the vaccine had killer lymphocytes not only in his pancreas, but also in his liver, which was apparently healthy, why? Apparently he had a non-cancerous lesion characterized by a mutation in the gene TP53, which is the same as in his pancreatic cancer. This suggests that the immune system activated by the vaccine could fight not only the primary tumor, but also metastasis in other organs.
Ignacio Melero, an expert in immunotherapy at the Clínica Universidad de Navarra, highlights the progress. “When the surgeon removes these tumors, residual disease usually remains. These results show us that it may make sense to add this vaccine, which is the first RNA vaccine that has shown positive results in the pancreas, to conventional treatments. An 18-month survival without relapse is a very respectable time”, he highlights. But the oncologist also warns that, for now, “the technology to develop these vaccines is very complex, especially since you have to do one per patient.” Although the pancreatic tumor is not one of the most common, only in 2020 more than 9,000 cases in Spain.
Ana Fernández-Montes, spokesperson for the Spanish Society of Medical Oncology, believes that this is a “very hopeful approach.” “We are talking about a tumor that after surgery can only receive chemotherapy to prevent recurrence, a treatment with a high failure rate and very significant toxicity,” she explains. “This treatment is a milestone in patients in whom it is possible to stimulate the T lymphocyte. We are converting a cold tumor, which does not respond to immunotherapy, into a hot one, which potentially will”, she adds.
Balachandran talks about the limitations of his job. “It is difficult to compare what we see in vaccinated patients with what we saw in long-term survivors, but we do know that the type of immune cells that are activated are the same: the CD8 killer T lymphocytes+”, he explains. The doctor says that this experimental vaccine must be further studied, slightly modifying the combination times with chemo and immunotherapy to see if effectiveness improves. They will also have to answer the most pressing question: why do only half of the patients react to the vaccine?
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