Supercharged mRNA vaccines boost T-cell response against cancer

A team of researchers from MIT, Harvard, and the University of Houston has developed an mRNA adjuvant that amplifies T-cell responses against tumors by up to 15 times. Successfully tested in mice, this approach could make cancer and infectious disease vaccines far more effective.

An mRNA adjuvant to boost immunity

Current cancer vaccines, such as those already approved by the FDA for certain melanomas or lung cancers, rely on activating the immune system. Their limitation: they do not always trigger a sufficient response. Conventional adjuvants, which are molecules that stimulate immunity, can also cause severe side effects.

Daniel Anderson’s team, a chemical engineer at MIT, offers an alternative. Their adjuvant consists of mRNA encoding two genes that activate signaling pathways in immune cells. Encapsulated in lipid nanoparticles, these mRNAs are injected alongside the vaccine.

In mice modeling bladder, colon, melanoma, or lung metastasis cancers, this approach slowed the growth of some tumors and eradicated others. Even without a vaccine targeting a specific antigen, the effect was visible. With a vaccine, the immune response was even stronger.

Promising results against cancer and viruses

The adjuvant also enhanced the effect of immune checkpoint inhibitors, drugs (such as pembrolizumab) that remove the brake tumor cells impose on T cells. These treatments, already approved for several cancers, could thus become more effective.

“The tumor microenvironment in solid tumors is often hostile to T cells, which is a major obstacle to immunotherapy. We observe that immune restructuring with these adjuvants creates a T cell-friendly environment and promotes tumor rejection.” — Christopher Garris, assistant professor at Harvard Medical SchoolTranslated from French

Another tested application: infectious diseases. When combined with Covid-19 or flu vaccines, the adjuvant generated a T-cell response 10 to 15 times higher than normal in mice.

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Next steps: toward clinical trials

The researchers now plan to test this approach on other animal models, with a view to developing it for cancer and infectious diseases. Meanwhile, another MIT team, led by Ana Jaklenec, is working on an adjuvant for the injectable polio vaccine to stimulate a mucosal immune response in the gastrointestinal tract — a key challenge for eradicating the disease.

If these results are confirmed in humans, mRNA vaccines could become a major weapon against cancer, with a dual advantage: increased efficacy and simplified production, thanks to the modularity of mRNA.