Researchers at Mass General Brigham are restoring the tumor cell’s own immune signaling by delivering cGAS mRNA via lipid nanoparticles to cancer cells, reactivating the cGAS-STING pathway to spur antitumor immunity.

This tumor-intrinsic strategy triggers immune responses including interferon production and activation of macrophages and dendritic cells, which then prime T cells to attack the cancer.

The work, led by Dr. Natalie Artzi on a multidisciplinary team, integrates molecular biology, immunology, nanotechnology and oncology to translate the concept into preclinical models.

The study builds on understanding tumor immune evasion and aims to counteract it by leveraging the tumor’s own signaling machinery.

The study was conducted in a mouse melanoma model and the findings are published in the Proceedings of the National Academy of Sciences in 2025.

In mice, a single treatment slowed tumor growth, while the combination with additional therapies produced the strongest anti-tumor effect.

The paper and related materials are accessible via Mass General Brigham and PNAS pages, with the PNAS DOI 10.1073/pnas.2409556122.

The research team’s approach combines biology, immunology, nanotech and oncology to move from concept to preclinical validation.

The publication details Restoration of cGAS in tumor cells promoting antitumor immunity via transfer of tumor-cell generated cGAMP in the tumor microenvironment.

Overall, this work points toward future cancer therapies that harness the body's natural defense by manipulating cancer-cell signaling to enhance immune recognition.

Next steps include developing systemic delivery options and testing combinations with DNA-damaging chemotherapy or radiotherapy to boost cGAMP production and cGAS-STING signaling.

Researchers plan to refine systemic delivery to reach non-accessible or metastatic tumors and to explore combining with chemo or radiotherapy for greater efficacy.