Of the more than 100 known types of cancer, pancreatic cancer is the deadliest. 88% of patients die despite receiving available treatments, mainly surgery and chemotherapy. There is a glaring downside to this horrible statistic: 12% of patients survive. Some live years, even more than a decade, without relapse. From a medical point of view, they are cured. How do you get it?
This question has inspired the development of an RNA-based vaccine against pancreatic cancer, the same molecule that enabled the development of immunizations against Covid in record time. The results of the first tests on patients – only 16 people in a first series of trials – have just shown promising results. In half of the patients, the vaccine succeeded in activating the immune system. None of them relapsed during the 18-month trial period. On the other hand, all patients who did not respond to vaccination suffered relapses.
The results are still very preliminary but represent an important milestone in an area where treatments and patient survival have barely improved over the past 40 years.
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Pancreatic cancer is the common cold tumor par excellence. In oncology jargon, this means the immune system is unable to recognize it and trigger inflammation – heat – to kill it. That is why immunotherapy, the most successful cancer treatment in recent years, does not work in the pancreas. What is surprising is that the tumors of the long-term survivors are on fire: they contain up to twelve times more immune cells than other patients. These 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 faulty proteins that the tumor produces – called neoantigens – and kill it.
“After analyzing samples from long-term survivors, we wondered if we could replicate it in the rest of the patients,” said Vinod Balachandran, a physician at Sloan Kettering Cancer Center in New York and leader of the team that developed the vaccine. explained to this newspaper. Most importantly, he believes, contrary to what was previously thought, pancreatic cancer produces molecules that enable the immune system to fight it.
The findings will be published this Wednesday in the journal Nature, a benchmark for the best world science. Along with Balachandran, they sign Ugur Sahin and Özlem Türeci, the already famous couple of Turkish descent who founded BioNTech and developed the successful RNA vaccine against Covid in collaboration with Pfizer. The truth is that both started their company with the very idea of having the first effective vaccines against cancer.
Researcher Vinod Balachandran, in New York in 2022.KarstenMoran (Karsten Moran)
In this complex clinical study, a vaccine had to be produced for each patient. After the tumors were removed from the abdomens of the 16 participants, the researchers sequenced their genomes and identified up to 20 neoantigens. Then they developed RNA vaccines that contained the recipe for each individual to synthesize their tumor’s specific molecules in their body.
At that point, they received 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 the aforementioned 50% of patients, the researchers observed that the number of killer lymphocytes in their bodies increased, which is likely the reason for the lack of recurrence. Balachandran explains that it hopes to start “soon” with BionTech the second phase of more detailed testing 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 pave the way for a second phase of clinical trials,” emphasize Amanda Huff and Neeha Zaidi, researchers from Johns Hopkins University (USA), who were not involved in the study, in a comment also published today. These cancer vaccine specialists point to an intriguing observation. One of the patients who responded to the vaccine had killer lymphocytes not only in his pancreas but also in his liver, which appeared healthy. Why? Apparently he had a benign lesion characterized by a mutation in the TP53 gene identical to the mutation in his pancreatic cancer. This suggests that the immune system activated by the vaccine could not only fight the primary tumor but also metastases in other organs.
Ignacio Melero, expert in immunotherapy at the Clínica Universidad de Navarra, highlights the progress. “When the surgeon removes these tumors, there is usually residual disease. These results tell us it might make sense to add this vaccine, which is the first RNA vaccine to show positive results in the pancreas, to conventional treatments. “A survival time of 18 months without recurrence is a very respectable time,” he emphasizes. However, the oncologist also warns that “the technology to develop these vaccines is currently very complex, especially because you have to make one per patient.” Although pancreatic tumors are not among the most common, more than 9,000 cases were reported in Spain in 2020 alone diagnosed.
Ana Fernández-Montes, spokeswoman for the Spanish Society for Medical Oncology, considers this 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 a very significant toxicity,” he explains. “This treatment is a milestone in patients where it is possible to stimulate T lymphocytes. We’re turning a cold tumor that doesn’t respond to immunotherapy into a hot tumor that might respond,” he adds.
Balachandran talks about the limitations of his job. “It’s difficult to compare what we’re seeing in vaccinated patients to what we’ve seen in long-term survivors, but we do know that the type of immune cell activated is the same: killer CD8+ T cells,” he explains . The doctor says this experimental vaccine needs further study, with slight adjustments to the combination times of chemotherapy and immunotherapy to see if effectiveness improves. You also need to answer the most pressing question: Why are only half the patients responding to the vaccine?
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