Vaccines that harness the immune system to fight cancer have shown clinical promise, but many patients fail to mount a strong enough response. Current efforts to boost immunity by co-delivering immune-stimulating molecules called cytokines often cause severe side effects. Now, a team led by MIT chemical engineer Daniel Anderson has reported a new strategy: using mRNA molecules to encode genetic adjuvants that switch immune cells into a more active state.
In a study published by the collaboration, which also includes researchers from Harvard Medical School and the University of Houston, the team designed mRNA sequences encoding two genes capable of turning on signaling pathways that activate T cells—key players in the immune response. When these mRNA adjuvants were packaged into lipid nanoparticles and injected into mice modeling bladder cancer, colon carcinoma, melanoma, and metastatic lung cancer, the treatment slowed tumor growth and eradicated many tumors, even without a cancer-antigen-specific vaccine.
“When these adjuvant mRNAs are included in the vaccines, the number of antigen-targeted T cells is substantially increased,” Anderson said. These T cells play a central role in the immune system’s ability to target and destroy cancer cells.
The mRNA adjuvant also enhanced the immune response to checkpoint blockade inhibitors, a class of FDA-approved immunotherapies that lift the brakes tumor cells place on T cells. “The microenvironment of solid tumors is often hostile to T cells and represents a major barrier to effective immunotherapy,” explained Christopher Garris, an assistant professor at Harvard Medical School and senior author of the paper. “We find that immune remodeling with these adjuvants creates a T-cell-permissive environment and promotes tumor rejection.”
Beyond cancer, the team tested the adjuvant with COVID-19 and flu vaccines in mice. They found that the mRNA particles boosted T-cell responses by 10 to 15 times compared to vaccines alone, suggesting the approach could also strengthen protection against infectious diseases.
The researchers plan to test the method in additional animal models before moving toward human trials. Meanwhile, a separate MIT group led by Ana Jaklenec has developed a different adjuvant to help injectable polio vaccine induce a strong mucosal immune response in the GI tract, potentially reducing viral shedding and transmission—a key goal in polio eradication.