Tumors in the human body contain immune cells—macrophages—that have the ability to fight cancer. However, the tumor microenvironment suppresses their activity, preventing them from performing their protective function. Researchers at KAIST have discovered a way to overcome this obstacle by directly converting macrophages already present within the tumor into active anti-cancer agents.

A New Approach to Therapy

The team, led by Professor Chi-Ho Park from the Department of Bioengineering and Brain Engineering at KAIST, has developed an innovative treatment method. By injecting a special preparation directly into the tumor, macrophages already present in the body absorb it and begin to produce CAR proteins—structures that recognize cancer cells. As a result, these macrophages become so-called CAR-macrophages, capable of effectively attacking the tumor.

Overcoming Tumor Barriers

Solid tumors, such as those found in the stomach, lungs, and liver, form dense structures that hinder the penetration and function of immune cells. Due to these physical and biological barriers, many existing immunotherapy methods are not very effective against such types of cancer. CAR-macrophages are considered a promising direction for next-generation immunotherapy, as they can not only directly destroy cancer cells but also activate neighboring immune cells, enhancing the body’s overall anti-cancer response.

Advantages of the New Method

Traditional CAR-macrophage therapy methods require extracting immune cells from the patient’s blood, cultivating and genetically modifying them in the laboratory, and then reintroducing them into the body. This process is complex, expensive, and difficult to scale, which limits its use for a wide range of patients.

To overcome these challenges, the KAIST team focused on so-called tumor-associated macrophages, which naturally accumulate around tumors. The researchers developed a way to reprogram these cells directly inside the body, eliminating the need for extraction.

Lipid Nanoparticle Technology

The core of the method is the use of lipid nanoparticles, which are easily absorbed by macrophages. These nanoparticles contain mRNA with instructions for recognizing cancer and a component that activates the immune system. This approach allows for the creation of CAR-macrophages by “directly transforming the body’s own macrophages into anti-cancer cells inside the body.”

After the preparation is injected into the tumor, macrophages quickly absorb the nanoparticles and start producing proteins that recognize cancer cells, while simultaneously activating immune signaling. The resulting “enhanced CAR-macrophages” show a significantly higher ability to destroy cancer cells and stimulate surrounding immune cells, leading to a powerful anti-tumor response.

Experimental Results

In animal experiments with melanoma—one of the most aggressive forms of skin cancer—tumor growth was noticeably slowed. Data also showed that the immune response could extend beyond the treated tumor, indicating the potential for broader protection of the body.

Professor Chi-Ho Park noted that this research introduces a new concept in immune cell therapy, where anti-cancer cells are formed directly within the patient’s body. He emphasized that this approach simultaneously addresses key limitations of existing CAR-macrophage methods—namely, delivery efficiency and overcoming the tumor’s immunosuppressive environment.