Beyond Covid-19

mRNA vaccines get ready for their next act: fighting cancer

When you look at the trajectory of the Covid-19 pandemic in the U.S., one turning point stands out: the availability of vaccines, predominantly the Pfizer-BioNTech and Moderna vaccines. Both use mRNA to send messages to cells about how to fight the deadly virus with incredible efficacy.

Though it feels like these messenger RNA vaccines quickly came to be, they weren’t developed overnight. For decades, scientists have been studying how to use mRNA to help the immune system fight cancer. And now that the Covid-19 vaccines have provided a greater understanding of mRNA’s superpower, many researchers are turning their focus back to developing mRNA tools to fight cancer.

mRNA tells cells which proteins to make — crucial information because proteins take care of everything from immune response to cell repair, which are essential processes for fighting cancer.

The mRNA vaccines have been heralded in cancer research. Compared to the politicized mRNA Covid-19 vaccines, “mRNA vaccines are looked at very differently — that is, positively — in the world of cancer,” says Sunandana Chandra, MD, associate professor in the division of hematology/oncology at Northwestern Medicine and a melanoma specialist at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

A form of immunotherapy

The National Cancer Institute currently has more than 20 phase 2 or phase 3 cancer vaccine clinical trials in progress. Most are mRNA-based. While some vaccines prevent viruses that cause cancer — such as vaccines to prevent HPV and hepatitis — others are treatment vaccines, training the immune system to attack cancer cells already in the body.

In cancer, mRNA vaccines are a form of immunotherapy — a growing branch of treatment that prompts the immune system to fight cancer in various ways.

Scientists are currently looking at mRNA vaccines for a variety of cancers, focusing on ones that they predict will elicit astrong immune response, such as melanoma, lung cancer, bladder cancer, and kidney cancer.

“mRNA-based therapies work by trying to turn on your own immune system to specifically get rid of a cancer.”

The mRNA vaccines work by instructing immune system cells to make proteins that will identify and attack cancer cells.“The more mutations you have,the more likely drug developers can develop a target against that mutated or otherwise altered gene,” says Chandra, who is currently leading the only phase 3 melanoma vaccine trial in Illinois.

The mRNA cancer vaccines would train the immune system to fight disease, in contrast to toxic chemotherapy that attempts to kill cancer cells, harming healthy cells in the process.

“I think that cancer is going to move away from a lot of the chemotherapy that has been used in the past and much more toward immuno-based therapies,” says Kathleen Mullane, DO, PharmD, an infectious disease specialist at the University of Chicago Medicine who has been involved in vaccine studies for Covid-19 and other diseases.

“The most promising thing is the toxicity appears to be lower for many of these agents when compared to conventional chemotherapy. Think of people having chemo — their hair may fall out, and bone marrow may be obliterated. In contrast, mRNA-based therapies work by trying to turn on your own immune system to specifically get rid of a cancer with the goal of not causing harm to noncancerous tissues,” she says.

Scientists have been working on this for decades. Back in 1990, University of Wisconsin researchers became the first to successfully transfer mRNA instructions they’d created into mice. Since then, researchers have refined mRNA development, focusing on infectious diseases and cancer.

That research proved essential in 2020, as scientists — with an influx of government funding — focused the mRNA platform on Covid-19.

“There’s no way [scientists] could have scaled up development and production of the Covid-19 vaccines without the previous research and knowledge gained from the cancer vaccines and other viral vaccines that were made in the past,” Mullane says. “The mRNA platform was made to be nimble, to rapidly produce effective and safe vaccines in the face of a pandemic.”

Simply plug in the right instructions to the body’s immune cells, and let a person develop their own immunity to fight the infection from there.

Lurking challenges

The mRNA vaccines for cancer introduce a few major challenges. First, there are more than 100 types of cancer, and each type has numerous subtypes. Each differs vastly, even within the same cancer type, so there’s no one vaccine that will fight all cancers.

“Cancer is so vast,” Mullane says. “It’s not one disease. Thereare a lot of mechanisms on which to target research work.”

And then there’s the financial burden. Unlike Covid-19, which everyone is potentially susceptible to, not everyone develops cancer. That means there’s less impetus for governmentsto subsidize development at the same level they did for Covid-19.

Compare money spent so far. For the 2021 fiscal year, the National Cancer Institute’s research budget is $6.56 billion. Meanwhile, through Operation Warp Speed, the government spent more than $19 billion on Covid-19 vaccine development. And that doesn’t include the cost of delivering and administering the vaccine.

Another major hurdle: the cost of producing mRNA vaccines.Standard vaccines use weakened or dead viruses and cost pennies per dose to produce, Mullane says.

Meanwhile, the infrastructure and materials needed to produce mRNA vaccines are significantly more expensive. The Pfizer and Moderna Covid-19 vaccines cost between $15 and $20 per dose, with government subsidies. That price will rise markedly without subsidies.

For cancer vaccines tailored to specific tumor types, the cost climbs even more, raising the question: Who will have access to them?

It’s too early to say.

Vaccine access

While the Covid-19 mRNA vaccine is now widely available, there won’t necessarily be the same easy access to cancer mRNA vaccines.

“Because of the technology and logistics required for this vaccine platform, it is inherently more challenging to offer to all patients. Which subset of our patients is this potentially a good approach for? How does it compare to our current standard of care? At this time, we don’t know the answer to that,” Chandra says.

Currently, the best way for a person with cancer to access mRNA cancer vaccine treatment is through clinical trials at academic medical centers. Search for trials online at clinicaltrials.gov, or talk with your oncologist.

The good news is that mRNA vaccines work. They work for Covid-19; they’re promising for cancer; and they may be used for other conditions, too.

“Hopefully, we’ll have something for HIV in the not-too-distantfuture,” Mullane says. “And if we have, say, a new swine flu variant for which the populace has no immunity, with this platform we can have a new effective and safe vaccine available in six months or maybe even quicker now that the technology is approved.”

It took a pandemic to launch mRNA vaccines onto the world’s stage. Now that they’re up and running, they’re bound to stay in the spotlight.