By Lisa Jarvis
Scientists are one step before completing a decades effort: to use vaccines to "train" our immune system to detect and destroy cancer cells.
The news that a mRNA vaccine against cancer, developed by Merck & Co. and Moderna Inc., prevented the recurrence of melanoma in a major final phase trial, marks the crucial next chapter for a technology found in the target of political reactions after the pandemic, after years of failed efforts.
The idea of cancer vaccines has been discussed here for more than a century, while in the last 20 years we have seen countless promising titles for "promising" initial stage treatments that have eventually been wrecked. Convincing the organization itself to fight its own battle proved much harder in practice.
The mRNA, however, finally brings this scientific industry out of the "hope" and "promise" stage. The Phase 3 study of Merck & Moderna, combining the individualised vaccine intismeran with keytruda immunotherapy, offers the necessary evidence to prove that cancer vaccines can actually work.
Much remains to be done to show whether their potential extends beyond melanoma and other forms of cancer. The data so far, however, justify enthusiasm – something that appeared on the Wall Street board, with Moderna's share price being more than doubled on Wednesday. Success in this test was decisive to prove that mRNA was not a "firework", useful only to combat infectious diseases. (Although, to be fair, there was a surprisingly effective tool that benefited billions of people around the world by coming out of the Covid-19 pandemic. )
Long before the word "Covid" entered our everyday vocabulary, the companies that developed mRNA technology focused on its potential against cancer. Indeed, Merck and Moderna have been working together to develop personalized cancer vaccines for more than a decade.
The logic of the vaccine sounds simple: Scientists genetically decode a patient's tumor to detect mutations that feed his cancer. MRNA strains bearing instructions to create these mutant proteins are then packed within a vaccine (intismeran contains mRNA strains that encode up to 34 of them). Think of it as giving immune cells a series of photographs of the "enemy", so that they know exactly who to attack – not only in the short term, but ideal for the next few years.
This is also the big bet of cancer vaccines: to rid patients of constant anxiety that their disease could at any time return aggressively. This vision now shows to be much closer to reality, although how close it remains to be seen. Merck and Moderna announced their findings through a press release, currently avoiding giving accurate data on the benefit size of intismeran for patients.
Nevertheless, what we know so far is impressive. The combination of the vaccine with Keytruda prolonged both the time to re-emergence of melanoma and the interval until metastases occurred. In June, the companies announced results from a smaller study following patients for a period of 5 years, finding that intismeran in combination with Keytruda therapy reduced the chances of recurrence or metastasis of melanoma by 49% compared to Keytruda alone.
In addition, Keytruda immunotherapy, the standard treatment for melanoma since 2014, has already improved and significantly prolongs people's lives. The cancer vaccine "went through an already high bar", said Michael Postow, head of the melanoma department at Memorial Sloan Kettering. "This is a very big achievement".
Merck plans to share the full data of the study on intismeran at an imminent medical conference or a scientific journal, and oncologists will study them thoroughly to understand not only how much more it can prevent the recurrence or spread of cancer, but also what groups of patients benefit the most. They will also seek evidence of how the vaccine is part of the existing therapeutic protocols.
In the short time since Merck and Moderna started this final stage test for intismeran, the treatment of melanoma continued to evolve. For years, patients were undergoing surgery to remove skin cancer and were then receiving immunotherapy to keep the disease under control. However, researchers recently found it more effective to start immunotherapy before surgery. Oncologists are now looking to see if adding the vaccine to post-operative immunotherapy offers even greater improvement, Postow said, who was one of the researchers in Merck's trial.
The most meaningful question, however, is whether mRNA can have the same effect on other types of cancer. Melanoma is considered by the "easy" targets for immunotherapy, because tumors are full of mutations, which facilitates the immune system to identify them as "invaders". Although some other cancers (such as lung, kidneys, and certain types of colon cancer) show similar sensitivity, the method does not work everywhere.
Nevertheless, oncologists hope that cancer vaccines, when added to other treatments, could strengthen the immune system enough to make the real difference for patients. Merck and Moderna have bet on testing this theory, investing in a series of final stage trials on lung, bladder and kidney cancer. Others turn to usually difficult tumors, such as pancreatic cancer, with encouraging first samples, although from very small studies.
Of course, the other question that hovers over this otherwise encouraging news is whether they will convince the several skeptics and conspirators that mRNA is not ultimately a malicious tool. The ideological wars surrounding technology have already jeopardised progress in cancer treatment. It took decades to reach today's evolution. It is time to put aside the unfounded political rhetoric so that patients do not have to wait so long for the next one.
