mRNA adjuvant boosts T cells in mice with cancer

The injections went into mice, not patients. But across models of bladder cancer, colon carcinoma, melanoma, metastatic lung cancer, and other tumors, an mRNA adjuvant helped the animals’ immune systems slow some cancers and eradicate many others. The work was led by MIT chemical engineer Daniel Anderson, with researchers from MIT, Harvard, and the University of Houston.

The problem is familiar in cancer immunology: vaccines can produce antibodies and T cells, but the response is sometimes too weak to control a tumor. Researchers have tried adding cytokines, molecules that stimulate immune activity, yet those combinations can cause severe side effects. Anderson’s team took a different approach, aiming to amplify the T-cell response directly.

The adjuvant contains mRNA molecules encoding two genes. Inside lipid nanoparticles, those instructions turn on signaling pathways that put immune cells into a more active state. The result is a more permissive environment for T cells inside solid tumors, according to Christopher Garris of Harvard Medical School, one of the paper’s senior authors. When the adjuvant was included with a vaccine targeting a cancer antigen, the number of antigen-targeted T cells rose substantially.

The effect was not limited to cancer. Given to mice alongside COVID or flu vaccines, the mRNA particles produced a T-cell response 10 to 15 times stronger than usual. The adjuvant also enhanced responses to checkpoint blockade inhibitors, drugs that work by lifting a brake tumors place on T cells and that are already FDA approved for several cancers.

So what does it change, concretely? If the findings hold up in further animal studies and eventually in people, the same adjuvant could make vaccines more effective against both tumors and viral infections without relying on the cytokine approach linked to severe side effects. For now, the cited results come from mice; the researchers plan to test additional animal models.