MIT researchers report mRNA adjuvant amplifies T-cell response against tumors
This digest was compiled by AI from multiple sources — links to the originals are below.
MIT chemical engineer Daniel Anderson and colleagues reported that an mRNA-encoded adjuvant substantially increased antigen-targeted T cells in mouse models of bladder cancer, colon carcinoma, melanoma, and metastatic lung cancer. Injections of lipid nanoparticles containing the adjuvant slowed tumor growth and eradicated many tumors, even without a cancer-specific vaccine. The adjuvant also boosted T-cell responses to covid and flu vaccines by 10 to 15 times.
Key Facts
- The mRNA adjuvant encodes two genes that switch immune cells into a more active state by turning on certain signaling pathways.
- In mouse models of bladder cancer, colon carcinoma, melanoma, and metastatic lung cancer, injections of lipid nanoparticles containing the adjuvant slowed tumor growth and eradicated many tumors.
- When delivered with covid or flu vaccines, the adjuvant generated a T-cell response 10 to 15 times stronger than usual.
- The adjuvant enhanced the immune response to checkpoint blockade inhibitors, FDA-approved immunotherapy drugs for several cancers.
- The researchers plan to test the approach in additional animal models for potential use in cancer and infectious diseases.
Adjuvant Mechanism
The new adjuvant consists of mRNA molecules encoding two genes that can switch immune cells into a more active state by turning on certain signaling pathways. Most vaccines generate not only antibodies but also T cells that can activate antigen-presenting cells, which help tell the immune system what to attack. The researchers boosted that response with the mRNA-encoded adjuvant, delivered via lipid nanoparticles.
Tumor Suppression Results
In studies of mice modeling bladder cancer, colon carcinoma, melanoma, metastatic lung cancer, and more, 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 when the mice were not given a vaccine against a specific cancer antigen, but when they were, the response was stronger still. The mRNA adjuvant also enhanced the immune response to immunotherapy drugs called checkpoint blockade inhibitors, which work by lifting a brake that tumor cells put on T cells and are FDA approved to treat several kinds of cancer. Christopher Garris, an assistant professor at Harvard Medical School and one of the paper’s senior authors, said the immune remodeling creates a T-cell-permissive environment and promotes tumor rejection.
Vaccine Enhancement
The researchers also explored whether their adjuvant could boost the immune response to vaccination against viral infection. When they delivered the mRNA particles to mice along with covid or flu vaccines, they found that the vaccine generated a T-cell response 10 to 15 times stronger than usual. The researchers now plan to test this approach in additional animal models, in hopes of developing it for use in both cancer and infectious diseases.
1 source
MIT researchers report mRNA adjuvant amplifies T-cell response against tumors
