A new cancer therapy wakes up immune cells inside tumors and turns them against cancer.

Tumors contain immune cells called macrophages that are naturally capable of attacking cancer. However, the tumor environment blocks these cells from functioning properly, preventing them from mounting an effective defense. Researchers at the Korea Advanced Institute of Science and Technology (KAIST) have now developed a new therapeutic strategy that overcomes this problem by transforming immune cells already inside tumors into active anticancer treatments.

KAIST Develops an In-Tumor Immune Cell Therapy

KAIST (President Kwang Hyung Lee) announced that a research team led by Professor Ji-Ho Park of the Department of Bio and Brain Engineering has created a new therapy that works directly at the tumor site. When the drug is injected into a tumor, macrophages already present in the body absorb it and begin producing CAR (a cancer-recognizing device) proteins on their own. This process converts them into anticancer immune cells known as “CAR-macrophages.”

Why Solid Tumors Resist Immune Treatments

Solid tumors — such as gastric, lung, and liver cancers — form dense structures that prevent immune cells from easily entering or maintaining their activity. Because immune cells struggle to reach and survive within these tumors, many existing immune-based cancer treatments have shown limited success.

The Unique Advantages of CAR-Macrophages

CAR-macrophages have recently gained attention as a next-generation immunotherapy. These cells can directly engulf cancer cells and also stimulate nearby immune cells, helping to strengthen and expand the body’s overall anticancer response.

Despite their promise, traditional CAR-macrophage therapies rely on extracting immune cells from a patient’s blood, growing them in the laboratory, and genetically modifying them before returning them to the body. This process is expensive, time-consuming, and difficult to apply widely in real-world clinical settings.

To overcome these challenges, the research team focused on “tumor-associated macrophages” that naturally accumulate around tumors. Instead of removing these cells, the scientists aimed to reprogram them directly within the body.

Lipid Nanoparticles Enable In-Body Reprogramming

The team developed a method that uses lipid nanoparticles — designed to be easily absorbed by macrophages — to deliver both mRNA containing cancer-recognition instructions and an immunostimulant that activates immune responses.

In this study, CAR-macrophages were generated by “directly converting the body’s own macrophages into anticancer cell therapies inside the body.”

Strong Anticancer Effects Observed in Tumors

After the therapeutic agent was injected into tumors, macrophages quickly took it up and began producing proteins that recognize cancer cells. At the same time, immune signaling pathways were activated. The resulting “enhanced CAR-macrophages” demonstrated significantly improved cancer cell-killing ability and stimulated surrounding immune cells, leading to a strong anticancer effect.

In animal models of melanoma (the most dangerous form of skin cancer), tumor growth was significantly reduced. The findings also suggested that the immune response could extend beyond the treated tumor, indicating the potential to trigger broader, body-wide immune protection.

A New Concept for Cancer Immunotherapy

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,” adding 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.ACS Nano.
DOI: 10.1021/acsnano.5c09138

The study was led by Jun-Hee Han, Ph.D., of the Department of Bio and Brain Engineering at KAIST as the first author. The research was published inACS Nanoan international journal specializing in nanotechnology.

The work was supported by the Mid-Career Researcher Program of the National Research Foundation of Korea.

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