KAIST Researchers Pioneer ‘CAR-Macrophage’ Therapy, Transforming Immune Cells Directly Within Tumors
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A groundbreaking new cancer treatment developed by researchers at the Korea Advanced Institute of Science and Technology (KAIST) offers a potential bypass to the challenges of existing immunotherapies. This innovative approach reprograms immune cells already present inside tumors, turning them into potent cancer fighters without the need for lengthy and expensive external cell manipulation.
The difficulty in treating solid tumors – including cancers of the gastric system, lungs, and liver – stems from their dense structure, which hinders immune cell access and function. Existing immunotherapies, while effective against some cancers, often struggle to penetrate these tightly packed masses. However, a team led by Professor Ji-Ho Park from KAIST’s Department of Bio and Brain Engineering has devised a strategy to overcome this obstacle.
Harnessing the Power of Macrophages
The research, announced by KAIST on Thursday, centers on macrophages, immune cells naturally equipped to attack cancer. Tumors, though, typically suppress macrophage activity, preventing them from fulfilling their cancer-fighting role. The KAIST team’s breakthrough lies in their ability to reactivate these suppressed cells.
When the newly developed treatment is injected into a tumor, macrophages absorb the therapeutic agent. These cells then independently produce CAR (chimeric antigen receptor) proteins – essentially cancer-recognition devices – transforming into highly targeted CAR-macrophages. Unlike some other immune cells, macrophages can directly engulf and destroy cancer cells, and also stimulate surrounding immune cells, amplifying the overall anticancer response.
Overcoming the Limitations of Existing CAR-Macrophage Therapies
Current CAR-macrophage therapies are hampered by a complex and costly process. They require the extraction of a patient’s immune cells, laboratory cultivation, genetic modification, and eventual reintroduction into the body. This process is not only expensive and time-consuming but also presents logistical hurdles for widespread clinical submission.
To address these limitations, the KAIST team focused on tumor-associated macrophages – immune cells that naturally accumulate around tumors. They developed a method to reprogram these cells in situ, eliminating the need for external manipulation.
Direct Reprogramming with Lipid Nanoparticles
The researchers engineered lipid nanoparticles designed to be readily absorbed by macrophages. These particles carry mRNA encoding cancer-recognition information, alongside an immune-boosting compound to stimulate cellular activity. This combination effectively “directly converts the body’s own macrophages into anticancer cell therapies inside the body,” according to professor Park.
Upon injection, the therapeutic agent is rapidly taken up by macrophages, initiating the production of cancer-recognizing proteins and activating crucial immune signaling pathways. The resulting “enhanced CAR-macrophages” demonstrate substantially increased cancer-killing activity and stimulate surrounding immune cells,triggering a robust anticancer response.
Promising Results in Melanoma Models
Initial studies, conducted on animal models of melanoma, the most dangerous form of skin cancer, yielded encouraging results. Tumor growth was substantially reduced, and the immune response extended beyond the injected tumor site, suggesting the potential for broader, systemic immune protection.
“This study presents a new concept of immune cell therapy that generates anticancer immune cells directly inside the patient’s body,” Professor Park stated. “It is notably meaningful in that it simultaneously overcomes the key limitations of existing CAR-macrophage therapies – delivery efficiency and the immunosuppressive tumor surroundings.”
The research, spearheaded by Jun-Hee Han, Ph.D., from KAIST’s Department of Bio and Brain engineering, was published in ACS Nano, a leading international journal focused on nanotechnology. The work was supported by the Mid-Career researcher program of the National Research Foundation of Korea.
