mRNA adjuvant boosts T-cell response to cancer vaccines

Researchers at MIT and other institutions developed an mRNA-based adjuvant that enhances T-cell activity against tumors. In mouse models, the approach slowed or eliminated several cancer types, and it also improved the effectiveness of checkpoint inhibitor drugs. The technique could lead to more potent cancer vaccines and stronger immune responses to infectious diseases.

The adjuvant works by delivering mRNA that encodes two genes capable of activating immune signaling pathways, packaged inside lipid nanoparticles. Unlike cytokine-based adjuvants, which often produce severe side effects, this approach appears to remodel the tumor microenvironment into a state more permissive to T-cell activity. In mouse models of bladder cancer, colon carcinoma, melanoma, and metastatic lung cancer, the treatment slowed or eliminated tumors, with the strongest effects seen when combined with antigen-specific vaccines.

Beyond oncology, the same mRNA adjuvant amplified T-cell responses to covid and flu vaccines by 10 to 15 times in mice. The research team, led by MIT's Daniel Anderson with collaborators at Harvard and the University of Houston, now plans to test the approach in additional animal models. Separately, MIT's Ana Jaklenec group has used a different adjuvant to help the injectable polio vaccine generate mucosal immunity in the GI tract, a response previously achieved mainly by the oral vaccine.