New therapeutic approach converts immune cells in tumors into cell therapies against cancer

New therapeutic approach converts immune cells in tumors into cell therapies against cancer

In tumors of the human body, there are immune cells (macrophages) that can fight cancer, but are unable to perform their tasks properly due to suppression by the tumor. KAIST researchers have overcome this limitation by developing a new therapeutic approach that converts immune cells in tumors directly into cancer 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 Biological and Brain Engineering has developed a therapy in which a drug, when injected directly into a tumor, is absorbed by macrophages already present in the body, independently produces CAR proteins (a cancer-detecting device), and is converted into anti-cancer immune cells known as “CAR macrophages”.

Solid tumors – such as stomach, 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 gained attention as a next-generation immunotherapy, have the advantage of directly enveloping cancer cells while simultaneously activating surrounding immune cells to enhance anticancer responses.

However, traditional CAR-macrophage therapies require the extraction of immune cells from a patient's blood, followed by cell culture and genetic modification. This process is time-consuming, expensive and can only be carried out to a limited extent in practice on patients.

To address this challenge, the research team focused on “tumor-associated macrophages,” which already accumulate around tumors.

They developed a strategy to directly reprogram immune cells in the body by loading lipid nanoparticles - designed to be easily absorbed by macrophages - with both mRNA, which encodes information for cancer detection, and an immune stimulant, which activates immune responses.

In other words, in this study, CAR macrophages were created by “directly converting the body’s own macrophages into anti-cancer cell therapies in the body.”

When this therapeutic agent was injected into tumors, macrophages quickly absorbed it and began producing proteins that recognize cancer cells, while simultaneously activating immune signals. As a result, the created “enhanced CAR macrophages” showed significantly improved ability to kill cancer cells and activated surrounding immune cells, resulting in a potent 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 and trigger systemic immune responses.

"This study introduces a new concept of immune cell therapy that generates anticancer immune cells directly in the patient's body," adding, "It is particularly significant because it simultaneously overcomes the key limitations of existing CAR-macrophage therapies - delivery efficiency and the immunosuppressive tumor environment."

Professor Ji Ho Park

This research was led by Jun-Hee Han, Ph.D., of the Department of Biological and Brain Engineering at KAIST as first author and the results were published on November 18 inACS Nanoan international journal in the field of nanotechnology.

This research was supported by the Mid-Career Researcher Program of the National Research Foundation of Korea.

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