New mRNA cancer vaccine targets lymph nodes for stronger immune response

Researchers at Tufts University have created a new mRNA vaccine for cancer that’s designed to carry its cargo to the lymph nodes rather than the liver. Tests in mice showed significant inhibition of the tumors, with the cancer disappearing completely in a decent percentage of cases.

Living cells produce proteins in structures known as ribosomes, according to instructions they receive from mRNA molecules. If you could deliver custom instructions to ribosomes, you could theoretically produce whatever proteins you needed – and that’s the idea behind mRNA therapies, which produce antigens that train the immune system to recognize invaders like viruses and mount an immune response.

Development on these therapies has greatly accelerated in recent years, thanks largely to the COVID-19 pandemic. The breakthrough is now opening up the possibility of mRNA therapies for a range of other diseases, including HIV, influenza, malaria, Lyme disease, herpes, shingles, or even to repair heart tissue after a heart attack.

Perhaps the most exciting target, however, is cancer. In this case, mRNA isn’t so much a preventative vaccine but a therapeutic one, administered to cancer patients to treat existing tumors and protect against recurrence or metastasis. Trials have shown the technology could pair well with other treatments like immunotherapy.

For the new study, the Tufts researchers investigated ways to improve the immune response by changing where the mRNA ends up in the body. The team says that in most cases, the mRNA tends to end up in the liver, but a more effective immune response would be produced by sending the molecules to the lymphatic system, where immune cells are directly trained to recognize intruders.

To do so, the scientists tweaked the recipe for the lipid nanoparticles that transport the mRNA. This causes different molecules from the bloodstream to gather on the surface of the particles, which in turn bind to receptors in different organs. After testing a few combinations of properties, the team created lipid nanoparticles that favored delivery to the lymph nodes over the liver by a three-to-one ratio.

There, the vaccine was taken up by around a third of dendritic cells and macrophages. These key immune cells train up B and T cells to target specific antigens, which results in a stronger immune response against cancer.

In tests in mice with metastatic melanoma, the team found that the treatment significantly inhibited the tumors, when combined with another treatment called anti-PD-1 therapy. Better yet, complete remission occurred in 40% of cases, and the cancer didn’t recur down the track – even after the scientists later injected them with metastatic tumor cells.

“Cancer vaccines have always been a challenge because tumor antigens don’t always look so ‘foreign’ like antigens on viruses and bacteria, and the tumors can actively inhibit the immune response,” said Jinjin Chen, an author of the study. “This cancer vaccine evokes a much stronger response and is capable of carrying mRNA for both large and small antigens. We are hoping that it could become a universal platform not only for cancer vaccines, but also for more effective vaccines against viruses and other pathogens.”

The breakthrough could add a new weapon to our growing arsenal of mRNA cancer treatments, several of which are already in human trials.

The research was published in the journal PNAS.

Source: Tufts University

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