research
<(From Left) Professor Ji-Ho Park, Dr. Jun-Hee Han from the Department of Bio and Brain Engineering>
Within tumors in the human body, there are immune cells (macrophages) capable of fighting cancer, but they have been unable to perform their roles properly due to suppression by the tumor. KAIST researchers have overcome this limitation by developing a new therapeutic approach that directly converts immune cells inside 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 Bio and Brain Engineering has developed a therapy in which, when a drug is injected directly into a tumor, macrophages already present in the body absorb it, produce CAR (a cancer-recognizing device) proteins on their own, and are converted into anticancer immune cells known as “CAR-macrophages.”
Solid tumors—such as gastric, 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, costly, and has limited feasibility for real-world patient applications.
To address this challenge, the research team focused on “tumor-associated macrophages” that are already accumulated around tumors.
They developed a strategy to directly reprogram immune cells in the body by loading lipid nanoparticles—designed to be readily absorbed by macrophages—with both 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 anticancer cell therapies inside the body.”
<Figure . Schematic illustration of the strategy for in vivo CAR-macrophage generation and cancer cell eradication via co-delivery of CAR mRNA and immunostimulants using lipid nanoparticles (LNPs)>
When this therapeutic agent was injected into tumors, macrophages rapidly absorbed it and began producing proteins that recognize cancer cells, while immune signaling was simultaneously activated. As a result, the generated “enhanced CAR-macrophages” showed markedly improved cancer cell–killing ability and activated surrounding immune cells, producing a powerful anticancer effect.
In animal models of melanoma (the most dangerous form of skin cancer), tumor growth was significantly suppressed, and the therapeutic effect was shown to have the potential to extend beyond the local tumor site to induce systemic immune responses.
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.”
This research was led by Jun-Hee Han, Ph.D., of the Department of Bio and Brain Engineering at KAIST as the first author, and the results were published on November 18 in ACS Nano, an international journal in the field of nanotechnology.
※ Paper title: “In Situ Chimeric Antigen Receptor Macrophage Therapy via Co-Delivery of mRNA and Immunostimulant,” Authors: Jun-Hee Han (first author), Erinn Fagan, Kyunghwan Yeom, Ji-Ho Park (corresponding author), DOI: 10.1021/acsnano.5c09138
This research was supported by the Mid-Career Researcher Program of the National Research Foundation of Korea.
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