The triumph of the first Covid vaccines raises hope to fight cancer

The first vaccines against Covid-19 are not just a milestone in the fight against the pandemic. They are also the springboard for unconventional technology that could one day defeat other ailments that have eluded doctors, from cancer to heart disease.

Injections from Moderna Inc. and a partnership of Pfizer Inc. and BioNTech SE use genetic material called messenger RNA to efficiently transform the body’s own cells in vaccine factories. The approach had never been used outside of clinical trials, and how well it worked against coronavirus surprised even some of its most enthusiastic backers.

Now, with one vaccine gaining US approval and the other very close, validation of the pandemic could open up a whole new field of medicine.

“We are now entering the era of mRNA therapeutics,” said Derrick Rossi, a former stem cell biologist at Harvard University who helped found Moderna in 2010. “The whole world has seen this. There is going to be more investment and more resources. “

In some ways, the global pandemic was the perfect testing ground for the new technology, as deep-pocketed supporters, including Pfizer, became more willing to take risks. But the effort was only possible because BioNTech and Moderna Inc. had worked on messenger RNA for years.

The technology instructs cells to produce any type of protein, transforming them into small drug or vaccine production lines. A major drawback is that messenger RNA is fragile and must reach cells before the body breaks it down. In the coronavirus vaccine, this is done by using a modified form of mRNA and coating it with fatty nanoparticles.

BioNTech CEO Ugur Sahin began studying cancer technology about two decades ago with his wife, Ozlem Tureci, an immunologist who co-founded the company. Sahin says his teams were able to move quickly on the Covid project by building on what they had learned from cancer vaccine development.

The resulting ability to evaluate multiple candidates in parallel was “really beautiful,” Sahin said in an interview.

The cancer field could see its first messenger RNA drug approvals in two to three years, according to Sahin. Meanwhile, Rossi predicts that virtually all infectious disease vaccines will use the technology within a decade or two, in part because it is so much faster and cheaper. The scientist still owns shares of Moderna, but is no longer affiliated with the company.

There is no guarantee that they are right. The risk of failure hangs over every scientific activity.

But in addition to cancer, mRNA companies like Moderna, BioNTech, Translate Bio Inc., and others are working to harness technology in flu vaccines, a treatment for heart failure, cystic fibrosis, a common pathogen called cytomegalovirus, and perhaps the biggest challenge of all: HIV. , which has eluded vaccine researchers for four decades.

Stephane Bancel, Moderna’s CEO, recalls warning his wife when she left a diagnostic company established nearly a decade ago that her new employer had a less than 5% chance of success. But if they did, he told her, the advantage would be enormous.

“It’s not going to be a one-drug company,” he recalled saying in a telephone interview. “Either we fail and it’s zero, or we succeed and it’s an industry.”

A relatively quick gain for messenger RNA could be better seasonal flu vaccines. Influenza kills up to 650,000 people each year, and existing vaccines are often only partially effective because production must begin about six months earlier, based on informed guesses from health officials about which strains are most likely to circulate at that time.

Production could start later and involve less guesswork with the mRNA. “If you get close to what the coronavirus vaccine shows, that would be a major improvement,” said Matthias Kromayer, partner at MIG AG, one of BioNTech’s early venture capital backers.

And if people need regular Covid booster shots, the flu shots could be combined with a coronavirus booster to eliminate all winter respiratory viral concerns in one go, according to Moderna’s Bancel.

More importantly, messenger RNA can help produce vaccines against viruses that have evaded conventional approaches. After Covid, Moderna’s most advanced program is a vaccine against cytomegalovirus, which can cause birth defects when transmitted from pregnant mother to fetus. Scientists have been trying to develop a vaccine against this virus for 50 years, but Moderna believes that mRNA technology gives it an advantage. The first results from the mid-stage trials are promising, and the final-stage trials could begin next year.

The company is also working on cancer vaccines with drugmaker Merck & Co. In a study released in November, a Moderna vaccine combined with Merck’s blockbuster immune drug Keytruda helped shrink tumors in 5 out of 10 patients. with advanced head and neck cancer.

In addition to Merck, other large pharmaceutical companies are participating, from AstraZeneca Plc to Roche Holding AG. There is no doubt that mRNA will be an important method in the future, according to Severin Schwan, CEO of Roche. Roche, one of the world’s largest manufacturers of cancer drugs, is working with BioNTech to develop personalized cancer vaccines.

“The door opens here,” Schwan said in an interview. “Now it is being confirmed again through Covid-19, because it is real clinical data. That’s a good reason to keep investing. “

However, in addition to Covid-19, nearly all mRNA drugs and vaccines remain in the early stages of human testing. And while recent success may bode well for other infectious disease vaccines, the implications in oncology are less clear because cancer has evolved numerous defenses to evade the immune system.

“We can’t just say that because we’ve seen validation in the mRNA vaccine field, any other mRNA vaccine will work too,” says BioNTech’s Sahin. “Each approach has to address different biological and medical challenges.”

Most of BioNTech’s research outside of Covid focuses on cancer. There, the idea is not to prevent the disease but to treat it. The company is testing several different approaches, in order to find tell-tale sequences in a person’s tumor and encode the mRNA to tell immune cells how to attack those tumor cells.

The cash flow from the success of the coronavirus vaccine will allow German biotechnology to also boost its trials with cancer patients. One of BioNTech’s cancer vaccines elicited strong responses and, in some cases, shrunk tumors in patients with advanced melanoma in an 89-person trial published this summer. The first efficacy data from cancer patient studies could come as early as late next year or early 2022, according to the CEO.

BioNTech is also working with the Bill and Melinda Gates Foundation on an mRNA approach to HIV, which has so far eluded vaccine researchers because the virus can hide inside cells. Human testing has yet to begin on the project.

Some potential future uses sound a bit like science fiction for now. BioNTech is conducting preliminary research on whether mRNA can be used to reprogram cells for regenerative medicine. In the future, scientists may also design specific nanoparticles that accumulate in particular types of tissue such as bone marrow, said Drew Weissman, an immunologist at the University of Pennsylvania who helped develop the mRNA technology used in both Pfizer-BioNTech and the Modern vaccinations That could allow doctors to treat genetic diseases like sickle cell anemia with a simple intravenous injection of targeted mRNA therapy.

“It has enormous potential,” Weissman said. “I can’t even make a list of how many different things could be used.”