Within tumors in the human body are immune cells (macrophages) that can fight cancer. However, they have been unable to perform their function properly due to suppression by the tumor. Researchers at KAIST have overcome this limitation by developing a new therapeutic approach that directly converts immune cells within tumors into cancer-inhibiting 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 a drug is directly injected into a tumor. The macrophages already present in the body absorb the drug, independently produce CAR proteins (a cancer recognition device), and are converted into cancer-inhibiting immune cells called 'CAR macrophages'.
Solid tumors, such as stomach, lung, and liver cancer, grow as dense masses, making it difficult for immune cells to penetrate or maintain their function within the tumors. Therefore, the effectiveness of existing immune cell therapies is limited.
CAR macrophages, which have recently garnered attention as a next-generation immunotherapy, offer the advantage of directly engulfing cancer cells while simultaneously activating surrounding immune cells to enhance anti-cancer responses.
However, conventional CAR macrophage therapies require the extraction of immune cells from the patient's blood, followed by cell culture and genetic modification. This process is time-consuming, costly, and only partially practical for patient application.
To address this challenge, the research team focused on 'tumor-associated macrophages,' which have already accumulated around tumors.
They developed a strategy for directly reprogramming immune cells within the body by loading lipid nanoparticles—designed to be easily absorbed by macrophages—with both mRNA encoding cancer-recognition information and an immunostimulant that activates immune responses.
In other words, this study generated CAR macrophages by 'directly converting the body's own macrophages into anti-cancer cell therapies within the body'.
After injecting this therapeutic agent into tumors, it was rapidly absorbed by macrophages and began producing proteins that recognize cancer cells, while simultaneously activating the immune response. The resulting 'enhanced CAR macrophages' demonstrated a significantly improved ability to kill cancer cells and activated surrounding immune cells, thereby achieving a potent anti-tumor 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 and trigger systemic immune responses.
