Tumors in the human body contain immune cells called macrophages that are naturally capable of attacking cancer. However, tumors suppress these cells, preventing them from carrying out their cancer-fighting role. Researchers at KAIST have now developed a new therapeutic strategy that bypasses this suppression by turning immune cells already inside tumors into active anticancer treatments.
KAIST (President Kwang Hyung Lee) announced on the 30th that a research team led by Professor Ji-Ho Park from the Department of Bio and Brain Engineering has created a therapy that works directly inside tumors. When the treatment is injected into a tumor, macrophages already present in the body absorb the drug. These cells then produce CAR (a cancer-recognizing device) proteins on their own and transform into cancer-targeting immune cells known as "CAR-macrophages."
Why Solid Tumors Are So Hard to Treat
Solid tumors -- such as gastric, lung, and liver cancers -- form tightly packed masses that are difficult for immune cells to enter or function within. This dense structure limits the effectiveness of many immune-based cancer treatments, even when those therapies work well against other types of cancer.
CAR-macrophages have recently drawn attention as a promising next-generation immunotherapy. Unlike some immune cells, macrophages can directly engulf cancer cells. They also activate nearby immune cells, strengthening the overall anticancer response.
Limits of Existing CAR-Macrophage Therapies
Despite their promise, current CAR-macrophage therapies face major hurdles. They require immune cells to be collected from a patient's blood, grown in a lab, and genetically modified before being returned to the body. This process is expensive, slow, and difficult to apply broadly in clinical settings.
To overcome these challenges, the KAIST team focused on tumor-associated macrophages that naturally gather around tumors.
Reprogramming Immune Cells Directly Inside the Body
The researchers developed a method to reprogram immune cells without removing them from the body. They designed lipid nanoparticles that macrophages readily absorb. These particles carry both mRNA that encodes cancer-recognition information and an immune-boosting compound that stimulates immune activity.
As a result, CAR-macrophages were generated by "directly converting the body's own macrophages into anticancer cell therapies inside the body."
When injected into tumors, the therapeutic agent was quickly taken up by macrophages. The cells began producing cancer-recognizing proteins while immune signaling pathways were activated at the same time. The newly formed "enhanced CAR-macrophages" showed much stronger cancer-killing activity and stimulated surrounding immune cells, leading to a powerful anticancer response.
Promising Results in Animal Studies
In animal models of melanoma (the most dangerous form of skin cancer), tumor growth was significantly reduced. The findings also showed that the immune response could extend beyond the injected tumor, suggesting the potential for broader, body-wide immune protection.
Professor Ji-Ho Park said, "This study presents a new concept of immune cell therapy that generates anticancer immune cells directly inside the patient's body," and added 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."
Reference:
Jun-Hee Han, Erinn Fagan, Kyunghwan Yeom, Ji-Ho Park. In Situ Chimeric Antigen Receptor Macrophage Therapy via Co-Delivery of mRNA and Immunostimulant. ACS Nano, 2025; 19 (48): 40798 DOI: 10.1021/acsnano.5c09138
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