They had been anticipated in December and now, at the annual conference of theAmerican Association for Cancer Research underway in Orlando (Florida), were officially presented. Let’s talk about the preliminary results of the study (phase 2b) on the new personalized mRNA vaccine, developed by Moderna, combined with a classic immunotherapy, and tested in patients with advanced melanoma. Well, data two years after administration show a 44% reduction in the risk of recurrence or death in those who received the combination compared to those who received immunotherapy alone.
What we know about the mRNA vaccine for melanoma
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Data from the mRNA vaccine and pembrolizumab study
The study, coordinated by the Perlmutter Cancer Center in New York, involved 157 women and men with stage III or IV melanoma, in which the disease had been surgically removed from the lymph nodes or other organs where it had spread (although the cancer had not is detectable after surgery, the risk of it returning remains high). Of these patients, 107 received the experimental vaccine (for now identified with the acronym mRNA-4157/V940) plus immunotherapy with pembrolizumab; the remaining 50 received pembrolizumab alone. Over the course of two years, 24 patients in the first group (22.4%) and 20 in the second group (40%) had a recurrence. An important difference therefore emerges in the risk of relapse: as much as 44%. The severe adverse effects – the researchers report – were similar in the two arms: fatigue was the one most associated with the vaccine.
“Our study shows that an mRNA vaccine, when used in combination with pembrolizumab, prolongs recurrence-free time or survival compared to pembrolizumab alone,” said Jeffrey Weber, senior study investigator and deputy director of the Perlmutter Cancer Center. The Phase 3 study is already planned and will involve several centers globally. In addition, the combination already received a Breakthrough Therapy designation from the Food and Drug Administration last February, which means that the results will be reviewed with some speed by the US regulatory agency.
How the personalized vaccine works
Just like the anti-Covid vaccine, the new product is also based on messenger RNA and is designed to teach our immune system to recognize specific proteins (called neoantigens) present, this time, on cancer cells instead of a virus. The vaccine is called personalized because it is developed from samples of the tumors removed in each patient. According to the researchers, it takes 6 to 8 weeks to prepare each product, which can recognize up to 34 different neoantigens.
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A research “old” of 50 years
“Many other research groups are working on therapeutic mRna vaccines and on the concept of stimulating the immune system against cancer, an approach that was actually imagined in laboratories about 50 years ago and which has its roots in the work of scientists such as Giorgio Parmiani, the father of tumor immunology in Italy and pioneer with others in the world of this science”, he tells Oncoline Lycia Rivoltini, Head of the Translational Immunology Structure at the National Cancer Institute of Milan: “So if from an immunological point of view we are not saying anything new, it is however true that we are finally getting to clinical trials”. What we are observing – underlines the researcher – is the result of fortunate and unfortunate events of recent times, such as the Covid-19 pandemic, which has cleared mRNA vaccine technology, demonstrating that it is valid and safe for millions of people . It is welcome, then, to take advantage of the investment made and use it for other pathologies, above all for cancer.
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Results that do not surprise immunologists
“For those who have always believed in it, the results of this study are not surprising – continues Rivoltini – On the other hand, on paper the ingredients are all there: first, melanoma is a neoplasm in which immunotherapy has long proved to be very effective ; secondly, a vaccine is being tested which does not always and only use the same antigen, but identifies the antigens actually present on the tumor cells in each patient; third, mRNA technology is exploited, which although not very powerful in creating immune memory, is efficient in stimulating a short-term response; fourth, the vaccine is combined with anti-PD-1 immunotherapy, which is the most logical thing to do, because it takes off the inhibitory brake on the immune system”.
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Caution is a must
Despite this, some caution must be exercised in evaluating the data, because when from phase 2 studies, conducted on a few patients, we move on to evaluating the effectiveness of a strategy on large numbers, the benefits are usually reduced. “I hope, in any case, that the opportunity to learn from any negative results will not be wasted, which often reveal much more than the positive ones on the biological mechanisms underlying the diseases. And I hope that companies don’t prevent researchers from studying what doesn’t work.”
Beyond this, the immunologist wonders about the real applicability and impact in terms of costs and logistics that a machine like the one needed to develop a personalized vaccine will be able to have in Italy: “I am thinking, for example, of the manipulation of samples tumors and their shipment to a centralized factory, probably overseas. If this type of vaccine, in the event of efficacy, were not to be developed in an ‘off-the-shelf’, i.e. ‘ready to use’ version, the commitment to a health system like ours is difficult to imagine” , concludes Rivoltini.