MIT researchers develop mRNA adjuvant to amplify T-cell response in cancer vaccines

Cancer vaccines that enlist the immune system against tumors have shown promise in clinical trials, and a few are FDA-approved for certain cancers. In many patients, however, the vaccines do not generate a strong enough response. One common strategy to strengthen them — delivering the vaccine with immune-stimulating molecules called cytokines — can cause severe side effects, the report says.

The MIT-led team took a different approach by amplifying T-cell response to mRNA vaccines. Most vaccines produce antibodies and T cells that can activate antigen-presenting cells, which help direct the immune system. The new adjuvant consists of mRNA molecules encoding two genes that switch immune cells into a more active state by turning on certain signaling pathways.

In studies of mice modeling bladder cancer, colon carcinoma, melanoma, metastatic lung cancer and other cancers, injections of lipid nanoparticles containing the mRNA-encoded adjuvant enabled the immune system to slow growth of some tumors and eradicate many others. This happened even without a vaccine against a specific cancer antigen; when a vaccine was included, the response was stronger.

Daniel Anderson, an MIT chemical engineer and one of the researchers, said: “When these adjuvant mRNAs are included in the vaccines, the number of antigen-targeted T cells is substantially increased. These T cells play an important role in the immune response.”

The mRNA adjuvant also enhanced the immune response to checkpoint blockade inhibitors, which lift a brake that tumor cells put on T cells and are FDA-approved for several cancers. Christopher Garris, an assistant professor at Harvard Medical School and a senior author of the paper, said: “The microenvironment of solid tumors is often hostile to T cells and represents a major barrier to effective immunotherapy. We find that immune remodeling with these adjuvants creates a T-cell-permissive environment and promotes tumor rejection.”

The researchers also tested the adjuvant with covid and flu vaccines in mice, finding that the vaccines generated T-cell responses 10 to 15 times stronger than usual. They now plan to test the approach in additional animal models with the goal of using it for cancer and infectious diseases.

The report also describes a separate project by a group led by Ana Jaklenec, a principal investigator at MIT’s Koch Institute for Integrative Cancer Research. Using an adjuvant, they helped the injectable polio vaccine induce strong mucosal immunity in the gastrointestinal tract, a response normally produced mainly by the oral vaccine. Many countries have stopped using oral polio vaccine because of rare risks not found in the injectable version.