Treatments based on the same messenger RNA technology (mRNA) that brought Covid-19 vaccines to market in record time are showing lasting benefits against melanoma, a lethal skin cancer, and showing early promise in pancreatic and brain cancers, once considered immune to attack by the immune system.
Advances in cancer vaccines – considered one of the fastest growing segments of oncology research – appear to be coming, even as US authorities send mixed signals about the merits and safety of this technology. More than 130 studies were presented at the American Society of Clinical Oncologyin Chicago, this month, focusing on these efforts.
At the forefront were Moderna and Merck, whose treatment combines a potent immunotherapy drug with an experimental vaccine (of mRNA made to order) against cancer kept melanoma at bay for five years, a milestone in efforts to create personalized vaccines to train the immune system to fight cancer cells.
These two companies are testing mRNA-based therapies in nine large and medium-sized trials in lung, kidney, bladder and pancreatic cancers, and may have the first results from their large confirmatory trial in melanoma this year.
Elsewhere, years of initial research at universities and medical centers have evolved into development programs at pharmaceutical companies like Roche and biotechnology company BioNTech.
Market research firm Vision Research Reports predicts that the market for personalized cancer vaccines, driven largely by mRNA technology, could reach $8.5 billion annually by 2034.
In infectious diseases, certain vaccines can teach the immune system to recognize and attack viruses, offering lasting protection. “This principle can now be applied to cancer, which is a major advance”, considers Eliav Barr, Medical Director at Merck.
These advances come even as the United States Department of Health and Human Services, led by anti-vaccine activist Robert F. Kennedy Jr. (RFK Jr.), cut $500 million from mRNA vaccine projects. RFK Jr. has attacked the safety and effectiveness of mRNA vaccines without evidence and has made exaggerated claims about side effects.
Still, the National Cancer Institute is collaborating with the US Foundation for the National Institutes of Health in a $200 million public-private partnership to fund trials of promising cancer vaccines, including those based on mRNA.
A spokesperson for Department of Health and Human Services defended Kennedy’s position on mRNA technology for infectious diseases, but said he sees promise in this technology for preventing cancer recurrence, pointing to the partnership for cancer vaccines.
However, dividing mRNA research into silos could delay progress on a promising technology that has been safely administered to more than 700 million people during the Covid-19 pandemic, scientists said.
“We have to be able to innovate around technologies that will improve healthcare for everyone,” says Elias Sayour, who runs an RNA engineering lab at the University of Florida (USA) and is a consultant for for vaccines for cancer in National Cancer Institute. “If we don’t do it, other countries will.”
From initial discovery to potential breakthrough
A decade ago, Vinod Balachandranof the Memorial Sloan Kettering Cancer Center, was one of the first scientists to see the potential of mRNA to treat even the most lethal cancers. He noticed that, in rare cases, some patients managed to survive pancreatic cancer, a disease that scientists believed was invisible to the immune system.
Studies revealed that, in these cases, the patients’ immune systems were able to recognize and attack their tumors. The question was how to make this more common.
Vinod Balachandran believes that mRNA, which can be produced quickly, could be used to design personalized vaccines based on specific genetic mutations found only in patients’ tumors after surgery.
A 16-patient phase 1 trial began in December 2019, testing a combination of chemotherapy, Roche’s immunotherapy Tecentriq (atezolizumab) and a custom-made mRNA vaccine from BioNTech that targets mutated proteins based on each patient’s tumors.
In April, at the meeting of the American Association for Cancer Research (AACR), Vinod Balachandran said that of the eight pancreatic cancer patients whose immune systems responded to the vaccine, seven were still alive six years later. A global phase 2 trial with 260 patients is now underway to confirm these results.
“It would be a major breakthrough if mRNA were the technology that could finally elicit a clinically meaningful immune response,” says Robert Vonderheide, director of the Cancer Center at Penn Medicine, a private hospital network in Philadelphia, and president-elect of the AACR.
THE software of the body
Messenger ribonucleic acid, or mRNA, is naturally present in every cell in the body. Its function is to carry genetic instructions from the cell nucleus to parts of the cell that produce specific proteins.
Elijah Sayour calls mRNA the software of the human body. It can be reprogrammed to perform a range of tasks, including producing proteins that train the immune system to attack infectious pathogens or rogue cancer cells, he highlights.
Research like this is being done at the Icahn School of Medicine at Mount Sinai in New York, where Brian Brown, director of the Icahn Institute for Genomics, has developed a method to grow lipid nanoparticles – bubbles of fat that carry mRNA into cells – to control where in the body they go.
One published study by the team of Brian Brown in the magazine Nature Biotechnologyin April, suggests that mRNA can be amplified or silenced to increase the immune response or attenuate harmful reactions, leading to more potent cancer treatments or new ways of treating autoimmune diseases.
Elijah Sayour has developed a vaccine that involves injecting clusters of lipid nanoparticles into patients with glioblastoma, rather than a single nanoparticle used in covid vaccines. Administered intravenously, the aim is to quickly stimulate the immune system to combat fast-growing brain cancer, whose 5-year survival rate is less than 7%.
Facing a cancer like glioblastoma It’s a difficult task for a vaccine, notes Elijah Sayour. But, according to him, “if we manage to cure or even make a dent in glioblastoma, the implications for all forms of human cancer are, in my opinion, extraordinary”.
