MIT Researchers Unveil Method to Activate Immune Response Against Tumors

Researchers at the Massachusetts Institute of Technology (MIT) have discovered a groundbreaking method to activate an immune pathway in tumors, potentially leading to their destruction. By stimulating cancer cells to produce a molecule that activates a specific signaling pathway in nearby immune cells, the team has found a way to trigger an immune response that can control tumor growth effectively.

The pathway in question is known as the cGAS-STING pathway, which plays a critical role in the immune response. In studies conducted on mice, the activation of this pathway proved to be significantly more effective when combined with existing immunotherapy drugs called checkpoint blockade inhibitors. This dual treatment not only controlled tumor growth but showed a remarkable ability to eradicate tumors in some instances.

The researchers achieved this activation by delivering messenger RNA (mRNA) that encodes the enzyme cGAS directly to cancer cells. This innovative approach avoids the need for large doses of a STING activator and leverages a natural process within the body. According to Natalie Artzi, a principal research scientist at MIT and the senior author of the study, “Our approach harnesses the tumor’s own machinery to produce immune-stimulating molecules, creating a powerful antitumor response.”

Mechanism Behind the Discovery

The cGAS enzyme catalyzes the production of a molecule known as cGAMP. When this enzyme detects double-stranded DNA, which can indicate either an infection or cancer-related damage, it activates the production of cGAMP. Tumor cells, due to their rapid and often inaccurate division, tend to release more double-stranded DNA fragments than healthy cells, making them prime targets for this therapy.

In their experiments, the MIT team injected mRNA encoding cGAS encapsulated in lipid nanoparticles into tumors in a mouse model of melanoma. Three groups of mice were treated: one received the mRNA alone, another received a checkpoint blockade inhibitor, and the third received both treatments. The results were promising; while both treatments slowed tumor growth individually, the combination led to complete tumor eradication in 30% of the mice.

This enhanced immune response was attributed to the production of interferons and other immune signaling molecules, activating various immune cells, including macrophages and dendritic cells. These cells play a crucial role in stimulating T cells, which are essential for destroying cancer cells.

Future Directions and Implications

The researchers are optimistic about the potential for this therapy to move into clinical use. They aim to adapt the delivery system for systemic injection, allowing for a broader application beyond direct tumor injection. Furthermore, they plan to investigate the combination of this mRNA therapy with chemotherapy or radiotherapy, which could enhance its effectiveness by increasing the availability of double-stranded DNA.

As noted by Alexander Cryer, a visiting scholar at the Institute for Medical Engineering and Science (IMES) and lead author of the study, “The side effects of this class of molecule can be pretty severe, and our approach has the potential to reduce some of the toxicity associated with direct administration of free molecules.”

The findings were published in the Proceedings of the National Academy of Sciences in 2025, and represent a significant advancement in cancer immunotherapy, moving closer to safer and more effective treatments for patients.

This research highlights a promising strategy to utilize the body’s immune system more effectively against cancer, paving the way for enhanced therapeutic options in the fight against this pervasive disease. More information can be found in the original study, which details the methodology and results of this innovative approach.