Will Federal Cuts Affect mRNA Cancer Vaccine Research?

Medscape

2 days ago

If you've ever administered or received a COVID-19 vaccine, chances are it was based on messenger RNA (mRNA) technology — a medical breakthrough decades in the making and finally achieved thanks to the coordinated effort and enormous funding mobilized by the pandemic.
The promise of mRNA vaccines is immense, researchers said. Several vaccines, including for influenza and respiratory syncytial virus, have been approved or are in the approval pipeline.
Now the same technology is being tested in hundreds of clinical trials for conditions that include not only infectious diseases but also many kinds of cancer.
And with the mRNA therapeutics market expected to grow to $30 billion by 2030, research momentum is strong — for now.
But recent cuts in federal research grants and the current administration's skepticism about mRNA vaccines have raised concerns that mRNA studies, including for cancer vaccines, could stall just as these treatments are starting to reach patients.
The Promise of mRNA Medicine for Cancer
Every gene in your body encodes an mRNA. It sends genetic information from the cell nucleus to the cytoplasm, where proteins are created to carry out the cell's work.
The lab-made mRNA used in vaccines tells the cell to make proteins that activate the desired response. The COVID-19 vaccine expresses COVID-19 genes, for instance, so the immune system learns to recognize and fight the virus.
In cancer cases, immune cells (T-cells) must be activated against a tumor. Checkpoint modulators allow the T-cell to penetrate the tumor and destroy it. The first of these immunologic drugs was approved in 2011, and since then, they have revolutionized treatment for '20% of all advanced, deadly cancers,' effectively turning them into chronic diseases, said Elizabeth Jaffee, MD, PhD, deputy director of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.
But in the other 80% of cases, she said, the immune system fails to generate the T-cells needed because it doesn't recognize the tumor cells as abnormal.
That's where mRNA could make a big impact.
Researchers at Johns Hopkins and elsewhere have developed a personalized approach. First, they biopsy the tumor and sequence the sample's genome. Based on that, they design an mRNA vaccine, which is then injected into the patient to trigger T-cells that recognize the tumor as abnormal. With the help of a checkpoint modulator, the T-cells can then attack and destroy the tumor.
The approach was tested at the Memorial Sloan Kettering Cancer Center, New York City, in an early clinical trial involving 16 patients with pancreatic cancer, which had a 5-year survival rate of 13%. Half of the participants received personalized mRNA vaccines, and the other half did not.
'3 years later, the eight patients who got the vaccine appear to have disease-free survival,' Jaffee said. 'If we can push this vaccine method forward, we'll definitely have an effect on cancer.'
Jaffee's team at Johns Hopkins is now conducting promising clinical trials on various gastrointestinal cancers — including colon cancer, gastric cancer, and a rare type of liver cancer.
But Jaffee fears she could get an email saying her National Institutes of Health (NIH) grant will be cutoff within 24 hours. 'We'll have to tell the patients that day, 'Sorry, we no longer have the money to treat you.' That would be devastating.' She says her team stands to lose $20 million in NIH funding — a gap they can't replace with private grants.
While the NIH hasn't officially pulled funding from mRNA research, scientists worry that it could be the next target in this year's wave of NIH cuts — concerns prompted in part by reports of funding cuts for vaccine hesitancy research and of NIH officials instructing scientists to scrub mRNA references from their grant applications.
Robert F. Kennedy, Jr, 'has been a strong critic of mRNA, and under his leadership, there have been emails asking for names of scientists working on mRNA research,' said Jeff Coller, PhD, professor of RNA biology and therapeutics at Johns Hopkins. 'This has been a pattern over the last few months. So we're concerned, and the industry is concerned.'
The Health and Human Services (HHS) Secretary has publicly expressed skepticism about vaccines, particularly the mRNA-based COVID-19 vaccines. In 2021, he described them as'the deadliest vaccine ever made.' That same year, the Children's Health Defense — a nonprofit organization that Kennedy founded and led before joining the Trump Administration — petitioned the US Food and Drug Administration (FDA) to rescind its authorization for the vaccines. Recently, the group has suggested a link between mRNA vaccines and cancer. Last week, the HHS canceled a nearly $600 million contract with mRNA vaccine maker Moderna for the development of its bird flu vaccine for humans.
The FDA has not yet approved any cancer vaccines, but one for late-stage melanoma, currently in a phase 3 clinical trial, is getting closer.
Some expect a successful trial will lead to FDA approval of the melanoma vaccine. But Drew Weissman, MD, PhD — who shared a Nobel Prize with Katalin Kariko, PhD, for the discoveries behind the COVID-19 vaccine — is less confident. As a vaccine researcher at the University of Pennsylvania, Philadelphia, leading a team of 80 scientists through dozens of trials, he worried that government skepticism could make FDA approval an uphill battle for his and others' mRNA research.
Who Will Pay for Cancer Vaccines?
The explosion in mRNA research has been funded by a mix of federal grants and private investment, with the government money aimed at basic research. The Defense Advanced Research Projects Agency had invested about $1 billion in mRNA research starting in 2012, said Andrew Geall, PhD, co-founder and chief development officer of Replicate Bioscience, an mRNA startup in San Diego. 'Most major pharmaceutical companies have made investments in mRNA technology,' said Geall. So have many venture capital firms. His own company, which was started in 2020, has received $53 million in private funding. This year, he said, Replicate Bioscience published phase 1 clinical trial data on its mRNA vaccine for rabies.
Moderna, one of the two major makers of COVID-19 vaccines, has conducted clinical trials on mRNA treatments for solid tumors. BioNTech, which codeveloped the other leading COVID-19 vaccine with Pfizer, is working on melanoma research. And Roche and Genentech are supporting Memorial Sloan Kettering's research on pancreatic cancer.
If NIH terminates mRNA grants, pharma companies and other US investors 'will probably pull back,' Geall said. That's because they rely on publicly funded research to share the costs — and risks — of their developments, he said.
In fact, private investment is already slowing down, as companies hedge their bets against an expected cutoff of mRNA research funding, Geall said. 'If we need to do clinical trials, we're probably going to go abroad.'
While most mRNA research is based in the United States, other countries are advancing studies of their own, poised to take the lead if the United States drops the ball. A recent poll showed that 75% of the US scientists will move abroad if their funding here is cutoff. Foreign regulators like the European Medicines Agency are gearing up to approve mRNA vaccines being developed in their countries.
If scientists in other nations develop new mRNA vaccines before our scientists do, their people would likely have access to mRNA vaccines sooner than Americans.
Whether any of this could delay US mRNA studies — and if so, for how long — remains unknown. After all, mRNA research is still happening in the United States, and with fruitful results.
If federal support for mRNA studies is cutoff, the research won't stop — at least, not 'in Europe or China' or elsewhere, Weissman said. 'But it's going to stop in the US'