Bloomberg解读Moderna与默沙东mRNA黑色素瘤癌症疫苗III期成功，股价已在首发日暴涨

The announcement by Moderna Inc. and Merck & Co. that a messenger RNA-based cancer vaccine had lowered the recurrence rate for melanoma in a final-stage trial is a watershed moment for cancer vaccine research. It’s the first time that an mRNA-based cancer vaccine has succeeded in a large-scale study. While the companies didn’t disclose details about the results, the success has bolstered hopes that mRNA-based shots could someday play a broad role in fighting one of the world’s leading causes of death.

The results also signal a second act for a technology that encountered widespread skepticism during the Covid-19 pandemic among those angered by vaccine mandates or uneasy about the shot’s rapid development. The technology continues to get pushback today, including from influential figures like US Health Secretary Robert F. Kennedy Jr.

But investors and many in the scientific community were cheered by the new findings. Moderna shares rose 177% the day the news was announced.

The results could boost enthusiasm for cancer vaccine research in general. Such vaccines have been pursued for decades by scientists, but they have frequently had lackluster results in all-important human trials.

How do mRNA vaccines work?

Traditionally, vaccines have worked by exposing the immune system to a weakened or inactivated form of a disease-causing organism, or to a harmless piece of one, so that the body learns to recognize and fight it.

Vaccines using mRNA take a different approach. They temporarily turn some of the body’s cells into tiny vaccine-making factories. The shots contain laboratory-made mRNA, which carries instructions telling those cells to make a particular protein associated with the disease. The immune system recognizes that protein and produces antibodies to attack it.

In the case of Covid vaccines, the mRNA instructs cells to make the spike protein found on the surface of SARS-CoV-2. That trains the immune system to recognize the spike and respond quickly if it later encounters the virus.

How can an mRNA vaccine treat cancer?

It turns out that essentially the same mRNA technology used for Covid and the flu – and being studied for other infectious diseases – can be employed to train the immune system to attack cancer. This type of vaccine isn’t used to prevent cancer but would instead be deployed to treat cancer already present, often to prevent a recurrence in patients who have had surgery. Such vaccines contain mRNA with instructions for making fragments of mutated proteins produced by cancer cells. Once inside the body, the mRNA instructs cells to produce the mutated protein fragments, so-called neoantigens. The goal is to prompt the immune system to recognize the mutated proteins, triggering an immune response against the cancer.

Why are mRNA vaccines personalized?

Cancer cells typically contain mutated proteins that, in theory, can be recognized by the immune system. But no two tumors are exactly the same, and mutations can vary widely among patients with the same type of cancer. Over the years, it has proven difficult to come up with a one-size-fits-all vaccine that consistently generates a strong immune system response against tumors, although researchers are still working on it. Among other problems, tumors might be able to evade an immune response targeted against a single distinguishing feature.

To create personalized vaccines, scientists take samples from an individual patient’s tumors and put it through an algorithm to determine which mutations are most likely to result in an immune response. For the Merck and Moderna shot, the companies can put up to 34 mutations into a personalized shot, which is sent back to the patient’s doctor to administer to the patient.

“Thirty-four is quite a lot of chances, of shots on goal,” said Jane Healy, head of oncology early development at Merck, which has been working with Moderna on the cancer vaccine approach for more than a decade. That ensures the vaccine is “covering a sufficient amount of the spectrum of a patient’s cancer.”

How are mRNA cancer vaccines different from other cancer treatments?

Cancer vaccines work in a very different way from other cancer treatments such as chemotherapy, targeted pills and immunotherapy. Chemotherapy poisons fast-dividing cells, while newer targeted medicines block particular growth-promoting proteins on cancer cells. Bestselling immunity-boosting drugs already on the market, including Merck’s Keytruda and Opdivo from Bristol Myers Squibb Co., are antibodies that disable a key method cancer cells use to evade an immune response against them.

But off-the-shelf immunotherapy drugs don’t prepare the immune system to recognize and target an individual’s specific tumor. This is what personalized cancer vaccines aim to do, which technically are treatments, not preventative shots.

Because it is thought this approach will work well against small volumes of cancer cells, many vaccines, such as the Merck-Moderna trial in melanoma, aim to prevent recurrences in patients who are at high risk of the cancer coming back after surgery.

Much is still unknown about the melanoma results, including the magnitude of the benefit. Findings from the vaccine trial will be reported at an upcoming scientific meeting. In particular, scientists don’t yet know whether people who got the vaccine will live longer, and the trial is continuing in order to gather long-term results.

What other diseases are mRNA treatments being tested against?

In addition to melanoma, Merck and Moderna are testing their personalized cancer approach for lung cancer, bladder tumors and kidney cancer. Meanwhile, Germany’s BioNTech SE and Swiss pharmaceutical giant Roche Holding AG are testing their own mRNA-based personalized cancer vaccine to treat both pancreatic cancer and colon cancer. BioNTech is working on a different mRNA technology that uses a standardized shot to treat patients with advanced lung cancer and head and neck cancer.

Rare diseases are another potential use for mRNA technology. Moderna is testing its mRNA technology to treat metabolic diseases including propionic acidemia and methylmalonic acidemia.