Researchers at KAIST have developed an injection that transforms immune cells within tumors into active cancer-killing agents, bypassing the need for complex lab procedures. The method uses lipid nanoparticles to deliver instructions directly to macrophages, enabling them to recognize and attack cancer cells while boosting broader immune responses. In animal tests, the approach significantly slowed tumor growth in melanoma models.
Solid tumors, such as those in gastric, lung, and liver cancers, pose significant challenges for immunotherapy due to their dense structures that hinder immune cell infiltration and function. Macrophages, immune cells naturally present in tumors, possess the ability to engulf and destroy cancer cells and to activate nearby immune defenses, but the tumor microenvironment typically suppresses them.
A team led by Professor Ji-Ho Park from KAIST's Department of Bio and Brain Engineering addressed these issues by developing a direct-injection therapy. The approach employs lipid nanoparticles loaded with mRNA encoding CAR proteins—chimeric antigen receptors that help cells identify cancer—and an immune-activating compound. When injected into the tumor, these nanoparticles are absorbed by tumor-associated macrophages, reprogramming them on-site into CAR-macrophages without the need to extract, modify, and reinfuse cells from the patient's blood.
This in situ reprogramming overcomes key limitations of traditional CAR-macrophage therapies, including high costs, lengthy processes, and poor delivery efficiency. In studies using animal models of melanoma, a severe form of skin cancer, the treatment markedly reduced tumor growth. It also triggered immune responses that appeared to extend beyond the injected site, hinting at potential systemic protection.
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." He further noted that the method "simultaneously overcomes the key limitations of existing CAR-macrophage therapies—delivery efficiency and the immunosuppressive tumor environment."
The research, with Jun-Hee Han as first author, was published on November 18, 2025, in ACS Nano. It received funding from the National Research Foundation of Korea's Mid-Career Researcher Program.
