Cancer vaccines that harness the immune system have shown promise and even gained FDA approval for certain cancers, but they often don't stir up enough of an immune response. Some researchers tried adding immune-stimulating molecules called cytokines to boost efficacy, only to find that approach can cause severe side effects - because of course it can.

Now, MIT chemical engineer Daniel Anderson and colleagues at MIT, Harvard, and the University of Houston have reported a different tactic: amplifying the T-cell response to mRNA vaccines. The advance could lead to more powerful cancer vaccines and stronger protection against infectious diseases - because who doesn't want that?

Most vaccines generate antibodies and T cells that activate antigen-presenting cells, which tell the immune system what to attack. In their study, the researchers boosted that response with a new vaccine adjuvant - a material that stimulates the immune system. This 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, and metastatic lung cancer, injections of lipid nanoparticles containing the mRNA-encoded adjuvant enabled the immune system to slow growth of some tumors and eradicate many others - even without a specific cancer vaccine. When a vaccine was given, the response was stronger still.

"When these adjuvant mRNAs are included in the vaccines, the number of antigen-targeted T cells is substantially increased," Anderson says. The mRNA adjuvant also enhanced the immune response to checkpoint blockade inhibitors, which lift the brake tumor cells put on T cells and are FDA approved for several cancers.

"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," says Christopher Garris, an assistant professor at Harvard Medical School and a senior author.

The researchers also tested the adjuvant with covid and flu vaccines in mice, finding it generated a T-cell response 10 to 15 times stronger than usual - because apparently, a 10-fold boost is just the beginning.

They now plan to test the approach in additional animal models, hoping to develop it for cancer and infectious diseases. Meanwhile, another MIT group led by Ana Jaklenec at the Koch Institute for Integrative Cancer Research has used an adjuvant to make the injectable polio vaccine induce a strong mucosal immune response in the GI tract - potentially reducing viral shedding and transmission without the rare risks of the oral vaccine that many countries have abandoned.