In tumors of the human body, there are immune cells (macrophages) capable of fighting cancer, but they have not been able to fulfill their role properly due to suppression by the tumor. KAIST researchers overcame this limitation by developing a new therapeutic approach that directly converts immune cells present in tumors into anticancer cell therapies.
KAIST (President Kwang Hyung Lee) announced on the 30th that a research team led by Professor Ji-Ho Park of the Department of Biotechnology and Brain Engineering has developed a therapy in which, when a drug is injected directly into a tumor, the macrophages already present in the body absorb it, produce CAR proteins (a cancer recognition device) themselves, and are converted into anti-cancer immune cells called “CAR-macrophages”.
Solid tumors, such as stomach, lung, and liver cancers, grow as dense masses, making it difficult for immune cells to infiltrate tumors or maintain their function. As a result, the effectiveness of existing immune cell therapies has been limited.
CAR-macrophages, which have recently attracted attention as a next-generation immunotherapy, have the advantage of directly engulfing cancer cells while simultaneously activating surrounding immune cells to amplify anticancer responses.
However, conventional CAR-macrophage therapies require immune cells to be extracted from a patient’s blood, followed by cell culture and genetic modification. This process is time-consuming, expensive, and has limited feasibility for real-world patient applications.
To address this challenge, the research team focused on “tumor-associated macrophages” already accumulated around tumors.
They developed a strategy to directly reprogram the body’s immune cells by loading lipid nanoparticles – designed to be easily taken up by macrophages – with both an mRNA encoding cancer recognition information and an immunostimulant that activates immune responses.
In other words, in this study, CAR-macrophages were created by “directly converting the body’s own macrophages into cancer cell therapies inside the body.”
When this therapeutic agent was injected into tumors, macrophages quickly took it up and began producing proteins that recognize cancer cells, while immune signaling was simultaneously activated. As a result, the generated “enhanced CAR-macrophages” showed significantly enhanced cancer cell killing ability and activated the surrounding immune cells, producing a powerful anti-cancer effect.
In animal models of melanoma (the most dangerous form of skin cancer), tumor growth was significantly suppressed and it was shown that the therapeutic effect could extend beyond the local tumor site to induce systemic immune responses.
This study presents a new concept of immune cell therapy that generates anti-cancer immune cells directly inside the patient’s body,” adding that “it is particularly significant in that it simultaneously overcomes the main limitations of existing CAR-macrophage therapies – delivery efficiency and immunosuppressive tumor environment.”
Professor Ji-Ho Park
This research was led by Jun-Hee Han, Ph.D., of the Department of Biotechnology and Brain Engineering at KAIST, as first author, and the results were published November 18 in ACS Nanoan international journal in the field of nanotechnology.
This research was supported by the Mid-Career Research Program of the National Research Foundation of Korea.
