Tumor-Infiltrating Macrophages Reprogrammed to Fight Cancer in Breakthrough KAIST Study

Researchers at the Korea Advanced Institute of Science and Technology (KAIST) have achieved a significant milestone in cancer immunotherapy by successfully reprogramming immune cells within tumors to actively fight cancer. This innovative approach overcomes a major hurdle in solid tumor treatment, where immune cells are often suppressed by the tumor environment. The findings, published in ACS Nano, offer a promising new direction for treating cancers like gastric, lung, and liver cancer.

The Challenge of Solid Tumor Immunotherapy

Solid tumors, characterized by their dense structure, pose a significant challenge to traditional immunotherapies. The physical barrier hinders immune cell infiltration, and the tumor microenvironment actively suppresses immune function. Existing CAR-macrophage therapies, while promising, require extracting, modifying, and reinfusing a patient’s own immune cells – a process that is time-consuming, costly, and not always feasible.

Reprogramming Macrophages In Situ

The KAIST research team, led by Professor Ji-Ho Park of the Department of Bio and Brain Engineering, focused on “tumor-associated macrophages” – immune cells already present within the tumor. Their breakthrough involves directly converting these macrophages into potent cancer fighters, eliminating the need for ex vivo manipulation.

The team developed a method using lipid nanoparticles designed to be readily absorbed by macrophages. These nanoparticles carry mRNA instructions for producing CAR (chimeric antigen receptor) proteins – essentially, cancer-recognition devices – and an immune-activating compound. Once inside the macrophages, the mRNA directs the cells to produce CAR proteins, transforming them into “CAR-macrophages.”

Enhanced Anticancer Response in Animal Models

In animal models of melanoma, the treatment demonstrated significant efficacy. The reprogrammed CAR-macrophages effectively recognized and destroyed cancer cells, while simultaneously activating surrounding immune cells to amplify the anticancer response. Researchers observed a notable reduction in tumor growth and evidence suggesting a broader, systemic immune response.

CAR-Macrophages: A Next-Generation Immunotherapy

CAR-macrophages offer several advantages over other immunotherapies. They can directly engulf and destroy cancer cells and stimulate surrounding immune cells, creating a powerful synergistic effect. This new approach addresses key limitations of existing CAR-macrophage therapies, namely delivery efficiency and overcoming the immunosuppressive tumor environment.

Future Directions and Implications

“This study presents a new concept of immune cell therapy that generates anticancer immune cells directly inside the patient’s body,” stated Professor Ji-Ho Park. The research opens avenues for more efficient and accessible cancer immunotherapies, potentially benefiting a wider range of patients. Further research will focus on optimizing the nanoparticle delivery system and expanding the application of this technology to other cancer types.

Study Details

The study was led by Dr. Jun-Hee Han from the Department of Bio and Brain Engineering at KAIST and was supported by the Mid-Career Researcher Program of the National Research Foundation of Korea. KAIST announced the findings on November 18, 2025.