Frankfurt Vaccines based on mRNA brought the breakthrough in the fight against the corona pandemic. Now the technology is also intended to decisively advance cancer therapy. Promising data are now available for the most important beacon of hope, a skin cancer vaccine: In patients whose tumors had previously been surgically removed, the active substance, in combination with the cancer immune drug Keytruda, reduced the risk of the cancer recurring by around 44 percent. This is shown by detailed data from a phase 2 study by the US biotech company Moderna and its partner Merck & Co. on the active substance called mRNA-4157.
The vaccine was tailored to the individual mutations in the patient’s tumors. Only 22.4 percent of the patients treated with the vaccine suffered a relapse within two years, compared to 40 percent in the comparison group. “The improvement in relapse-free survival rates suggests that the combination may offer a new opportunity to extend the lives of melanoma patients,” said Kyle Holen, Moderna’s director of oncology research.
Moderna and Merck confirmed their plans to quickly start a larger phase 3 study and also test the drug in other types of cancer. At the same time, Moderna apparently also wants to explore the possibility of accelerated approval based on previous data, as research head Stephen Hoge recently indicated at an analyst conference.
FDA designates vaccine as a breakthrough therapy
The approval authorities have already classified the new development as a potentially important innovation. In view of the data, the US Food and Drug Administration (FDA) rates the mRNA vaccine as a breakthrough therapy. The European medicines agency Ema included the product in its Prime program, under which the agency offers additional advice and support to speed up approvals.
The active substance from Moderna could thus become the first approved mRNA vaccine against cancer. That would be an important milestone for the technology, which has so far been struggling in oncology. For example, the Tübingen-based biotech company Curevac, long considered an mRNA pioneer, has ended almost all of its previous cancer projects without success. Moderna and Biontech, which started later, are now driving a whole series of projects in clinical studies.
It remains difficult to estimate to what extent mRNA will be able to assert itself in cancer therapy on a broader front. There is some evidence that it could become a valuable addition, but only for certain patient groups and in conjunction with other drugs. “It will be important to position cancer vaccines in such a way that they can do their job,” says Biontech boss Ugur Sahin.
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From his point of view, the optimal field of application will be in the adjuvant therapy of cancer diseases, i.e. in the treatment of patients who have already been successfully operated on, in order to reduce the risk of the disease recurring.
Around two dozen clinical studies with mRNA-based cancer therapies are currently listed in the clinicaltrials.gov database. Most of these are operated by the two mRNA specialists Biontech (eleven products in 14 studies) and Moderna (five products). In addition, some smaller biotech companies such as Ethris and Stemirna as well as academic institutions are also testing mRNA products in cancer treatment.
mRNA could significantly advance cancer therapy
The mRNA technique is particularly interesting for oncology because of its functionality and flexibility. The “messenger RNA” provides a template for protein synthesis – it can in principle stimulate the production of any type of protein in the body’s cells.
Researchers are therefore trying to use mRNA for cancer treatment: On the one hand, by using it as a therapeutic vaccine to activate existing endogenous immune cells against the cancer cells. On the other hand, to stimulate the production of anti-cancer substances, such as certain antibodies, in the body cells. mRNA could also be useful as an aid and supplement for cell therapies against cancer.
Development of mRNA anti-cancer drugs is difficult
However, the development of mRNA drugs presents significant challenges. The immune cells have to be activated strongly enough to fight the cancer. Curevac’s corona vaccine candidate, for example, failed to activate the immune cells sufficiently.
In addition, there are the difficulties of all cancer drugs: They are only intended to attack the tumors, but not the healthy rest of the body. To do this, the active ingredients have to act on the right molecular targets, i.e. on antigens that only appear on tumor cells but not on healthy cells.
Many tumor cells also develop defense mechanisms against the immune system. So even if it is possible to activate immune cells with mRNA-based cancer vaccines and to give them a genetic profile of the tumor cells, they will be deactivated in the vicinity of the cancer cells by molecular stop signals, so-called “checkpoints”, and remain ineffective.
In most studies, mRNA cancer vaccines are now being tested in combination with another class of cancer immune drugs that specifically target the defense mechanisms of cancer cells. Moderna is therefore testing its mRNA vaccine together with the checkpoint inhibitor Keytruda developed by Merck & Co.
Investors remain skeptical
So far, investors’ confidence in mRNA in cancer therapy has been limited. The valuations of Moderna and Biontech, for example, have so far hardly been shaped by their oncology research, but primarily by their Covid business and their vaccine activities in the field of infectious diseases.
After the announcement of the first positive data from the study with mRNA-4157, which is now presented in more detail, the Moderna share recorded a jump in price of around 25 percent in mid-December, but was unable to maintain these price gains.
Even in the research and acquisition strategies of the large pharmaceutical companies, mRNA is not in the foreground. Industry leader Pfizer, for example, recently increased its oncology activities with the $43 billion takeover of the US company Seagen in the field of antibody-drug conjugates. Biontech has also recently expanded its cancer research through deals outside of mRNA technology.
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