KAIST study reprograms tumor macrophages for cancer therapy

Within many solid tumors, immune cells known as macrophages are already present but are unable to perform their anticancer function effectively. Tumor-induced suppression limits their activity and reduces the impact of established immune cell therapies. According to a press release from the Korea Advanced Institute of Science and Technology (KAIST), researchers have now developed a strategy to activate these dormant immune cells directly inside tumors.

The research was conducted by a team led by Professor Ji-Ho Park from the Department of Bio and Brain Engineering at KAIST. The approach focuses on tumor-associated macrophages, which naturally accumulate in and around tumors but are usually rendered inactive.

The KAIST team developed a therapy in which a drug is injected directly into the tumor. Macrophages already present in the tissue absorb the drug and begin producing chimeric antigen receptor (CAR) proteins. As a result, they are converted into so-called CAR-macrophages, immune cells capable of recognizing and attacking cancer cells.

Solid tumors such as gastric, lung, and liver cancers often form dense tissue structures. These structures hinder immune cell infiltration and limit the effectiveness of conventional immunotherapies. CAR-macrophages are considered particularly suitable for these environments because they can directly engulf cancer cells and activate surrounding immune cells at the same time.

Conventional CAR-macrophage therapies require immune cells to be extracted from a patient’s blood, genetically modified in the laboratory, and expanded before being reintroduced. This process is time-consuming, costly, and difficult to implement widely in clinical practice.

To address these challenges, the researcher designed lipid nanoparticles that are readily absorbed by macrophages. These nanoparticles carry:

• mRNA encoding cancer-recognition information
• an immunostimulant to activate immune responses

This combination allows immune cells to be reprogrammed directly inside the patient’s body.

When the therapeutic agent was injected into tumors, macrophages rapidly absorbed it and began producing cancer-recognizing proteins. Immune signaling pathways were activated simultaneously. The resulting “enhanced CAR-macrophages” showed a increased ability to kill cancer cells and stimulated surrounding immune cells. In animal models of melanoma, tumor growth was suppressed.

Professor Ji-Ho Park stated, “This study presents a new concept of immune cell therapy that generates anticancer immune cells directly inside the patient’s body,” adding that “it is particularly meaningful in that it simultaneously overcomes the key limitations of existing CAR-macrophage therapies—delivery efficiency and the immunosuppressive tumor environment.”

MEDICA-tradefair.com; Source: KAIST (Korea Advanced Institute of Science and Technology)