The sample is small, the follow-up limited, but the results are encouraging: personalized mRna vaccines could also work against pancreatic cancer. If, on the one hand, it is perfectly right to consider the results from the Memorial Sloan Kettering Cancer Center in New York as preliminary, on the other, it is impossible to ignore them, above all because pancreatic cancer is one of the most difficult to eradicate with the therapies available today. . And the results say that mRna vaccines are able to induce an immune response against the tumor and seem to lengthen the relapse times. The details, already anticipated at last year’s Asco congress, are on pages of Natures.
mRNA vaccines against cancer
There has been a lot of talk about mRNA vaccines, especially in recent times, after the announcement by (Modern) industry exponents of the arrival, within just five years, of the first products against different types of cancer. We are talking about therapeutic vaccines, developed to instruct the immune system to fight cancer cells more strongly. And above all of personalized vaccines, packaged starting from the patient’s tumor cell antigens (so-called neoantigens). All thanks to the same technology that brought us the main vaccines against Covid: the instructions for the production of these neoantigens that serve to educate the immune system are written in the form of mRna, packaged inside particles then infused into patients. Technology, in the field of tumors, has already given encouraging results against melanoma, in combination with immunotherapy, and the hope is that it can also find confirmations for other locations and perhaps for tumors that are difficult to fight with more traditional weapons. Pancreatic cancer, with a very high relapse rate following surgery and a five-year survival of only 12%, is one of them.
After melanoma, the trials against pancreatic cancer
New York researchers – in collaboration with the companies BioNTech and Genentech – have developed a vaccine against pancreatic cancer, ductal adenocarcinoma, the most common form of the disease. The personalized vaccines for each patient were in fact synthesized starting from the neoantigens identified following the resection and molecular analysis of the tumor cells, and were administered within a combined treatment scheme. In fact, the patients – 16 included in the phase I study, to test the safety and tolerability of the therapy – first received immunotherapy (an immune checkpoint inhibitor, atezolizumab), then the vaccine and then chemotherapy. The idea was to understand if the vaccine, combined with other therapies, was safe and if it could induce a specific immune response against the tumor, and if this could delay the reappearance of the disease. And so it was, but not in all patients treated.
Melanoma, the first data on the combination of the mRNA vaccine and immunotherapy are positive
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The mRNA vaccine (generally well tolerated, only one patient developed a high-grade adverse event in response to the vaccine) induced the production of tumor-specific T lymphocytes in half of the patients, but not only. These T cells were detectable in patients’ blood for a long time, up to two years after vaccination, and their presence was associated with a better prognosis. Specifically, at an interval of 18 months, patients in whom the vaccine had induced an immune response had a longer median relapse-free survival (not actually reaching it, write the authors), compared to the rest, where it was around 13 months approximately. This suggests, the authors write, that T lymphocyte response may be associated with more favorable clinical outcomes for patients, thanks to specific tumor activity. “In particular, the case reported by the authors is suggestive of a single patient in whom after vaccination a hepatic lesion appeared who, after being biopsied, showed a lymphocytic infiltrate with specific clones for a specific mutation of the tumor of the patient, suggesting the ability of T lymphocytes to control micrometastases”, comments Nicola Silvestris, member of the national board of Aiom and full professor of medical oncology at the University of Messina.
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New trials against pancreatic cancer
The data collected suggest that mRna technology could work against pancreatic cancer, long considered unsuitable for immunotherapy strategies because it is relatively low in neoantigens compared to other tumors, explain Amanda L. Huff and Neeha Zaidi in an article commenting on the paper, in the same issue of Nature. “These data are extremely encouraging and will help lay the foundations for another clinical trial – write the experts – the researchers have shown that it is possible to use mRNA-based vaccines against pancreatic cancer, a disease previously considered too aggressive to personalized therapies”.
Of the same opinion Silvestris, who however underlines the limited number of patients included in the trial and the need for further studies to confirm what to date can only be considered as preliminary evidence. “But in a scenario, such as that of pancreatic cancer, where we have very blunt weapons and where until now immunotherapy strategies have not given significant advantages in terms of survival, the results reported today in Nature are intriguing – continues Silvestris – Si opens up a new scenario, potentially able to offer an important advantage in terms of survival free from disease recurrence”. Even if for now not all patients seem to respond, as shown in the study, which is why, the authors conclude, it could be useful to identify any markers capable of predicting which patients may respond to the vaccine and which may not.