The idea of using i mRNA vaccines For fight cancer It’s not new at all. After years of substantial failures we are at a turning point. Thanks to the improvement of the technology in question, the use of this approach is starting to give concrete results. The latest in chronological order are the studies presented at the recent congress ofAmerican Association for Cancer Research (AACR) held in San Diego. The vaccines a mRNA have proven useful in treatment of head and neck tumors It is in the pancreatic cancerespecially in theavoid post-operative recurrences.
TECHNOLOGY
mRNA vaccines have revolutionized the history of pandemic. An almost “fortuitous” event because in reality they were initially studied, starting from the last decade, as a therapeutic weapon against cancer. Now, thanks to their use for Covid-19, there has been renewed interest in mRNA vaccines against cancer. If for Covid-19 it was preventive vaccinesin this case – it is worth clarifying – we are talking about therapeutic vaccines. These, by stimulating the immune system, are used to trigger an immune response directed against tumor cells. If for Covid-19 the mRNA was injected to produce the spike protein and thus generate antibodies against it, the therapeutic cancer vaccines they trigger a response against a specific protein (tumor antigen) of the cancer cell which is absent in healthy cells. In this way the immune system fights the tumor while sparing everything else.
THE FAILURES
The basic idea is therefore simple. Why then has it never been possible to put it into practice until today? To explain it – as told in a previous article of ours – is Michele Maio, professor of Oncology at the University of Siena, director of the Immuno-Oncology Center at the Le Scotte Polyclinic hospital in Siena and president of the NIBIT Foundation: «In the past the clinical trials with therapeutic vaccinesused alone, have unfortunately had mixed success for the most part limited technological and immunological knowledge, which is due to a methodological error of approach. In fact, in recent years the effectiveness of these therapeutic tools capable of acting on the immune system was evaluated according to the typical criteria of the classic chemotherapy, such as the ability to reduce the tumor mass within a certain time window. Over the years we have understood that immunotherapy drugs, and even more so therapeutic vaccines which require more time to act, were necessary change the method with which to evaluate its clinical effectiveness. Now, thanks to the pandemic which has also been controlled thanks to mRNA vaccines, there has been renewed interest in these therapeutic agents against cancer.”
RESULTS IN MELANOMA
The first promising results presented last year concern the melanoma. Moderna and MSD presented the results of one of the most advanced studies, KEYNOTE-942, concerning stage III/IV melanoma at high risk of recurrence. In the trial, scientists compared the use of pembrolizumab alone – an immunotherapy already in use for many tumors – with the combination of pembrolizumab and mRNA-4157/V940, the vaccine created to stimulate the response against some typical melanoma proteins. The patients involved were people with stage III/IV melanoma who had had their tumor completely removed. From the analyzes of the phase IIb study – therefore not yet exhaustive – it emerged that the combination of the two strategies in adjuvant mode (i.e. to prevent the disease from recurring, a strategy already used successfully in melanoma) led to a reduction of the risk of relapse and death by 44% compared to pembrolizumab alone.
THE STUDY IN HEAD AND NECK CANCERS
Another vaccine being tested is the one developed by the French biotech company Transgene for head and neck tumors. The promising results were announced at the AACR conference. The study involved 33 patients with this type of neoplasm and had the aim of evaluating the ability of the mRNA vaccine TG4050 to prevent the development of recurrences immediately after surgery, i.e. in the adjuvant modality. Half of the patients were administered the vaccine after surgery, the others received it only in the event of an actual recurrence. The analyzes showed that 16 months after the operation, no person who received the vaccine developed a recurrence compared to the three cases of cancer in the non-vaccinated group. What has been obtained, due to the small number of numbers, does not yet demonstrate the effectiveness of the vaccine in prevent relapses but the signs are all there. In fact, in vaccinated patients the presence of immune system cells capable of recognizing tumor antigens was found.
THE BENEFITS IN PANCREAS CANCER
The other big news concerns the therapeutic vaccine against pancreatic cancer. BioNTech and Genentech, the companies producing the vaccine, presented the results at AACR on the use of the mRNA vaccine – always administered in adjuvant modality after surgery – in combination with chemotherapy and immunotherapy. The analyzes showed that after a year and a half, 8 out of 16 patients had developed an immune response against the tumor. Of these only two had a recurrence. By contrast, 7 of the 8 patients who did not develop a response relapsed. An important result, also in this case preliminary, which clearly indicates the possibility of reduce the risk of cancer if the person manages to develop an adequate immune response. To understand the significance of the result even more, just think that relapses generally develop within a year. In the study the duration of observation was 18 months.
FUTURE PERSPECTIVES
What has been achieved in these studies certainly does not represent the solution to the cancer problem. But compared to the past, where mRNA vaccines have always failed, we are faced with one watershed. Although there is still much to prove, the data is beginning to clearly indicate the usefulness of using this approach especially in adjuvant modality. According to experts, in fact, removing the tumor could reduce the disease’s ability to suppress the immune response. In this way, a favorable environment would be created to trigger an effective response against residual cells (those that can generate metastases and relapses) induced by the vaccine. At present there are many experiments underway whose results are expected in the next few years.
Tags: additional weapon cancer mRNA vaccines
