Cancer treatment has made great progress over the past few decades, but many solid tumors remain very difficult to treat.
Tumors in organs such as the stomach, lungs, and liver often grow into dense masses that protect cancer cells from the body’s immune system.
Even though immune cells are present inside these tumors, the cancer environment weakens them and stops them from doing their job.
Among these immune cells are macrophages. Macrophages are natural defenders of the body. Their normal role is to find, surround, and destroy harmful cells, bacteria, and debris.
In theory, macrophages inside tumors should be able to attack cancer cells. In reality, tumors create a hostile environment that suppresses these macrophages and turns them inactive or even supportive of tumor growth.
A research team at the Korea Advanced Institute of Science and Technology, known as KAIST, has now discovered a way to reverse this process. Instead of removing immune cells from the body and modifying them in a laboratory, the scientists found a method to reprogram immune cells directly inside tumors, turning them into powerful cancer-fighting cells.
The research team was led by Professor Ji-Ho Park from the Department of Bio and Brain Engineering at KAIST. Their approach focuses on immune cells that already exist inside tumors, called tumor-associated macrophages. These cells naturally gather around cancer but are usually disabled by the tumor environment.
The researchers developed a special drug delivery system that can be injected directly into a tumor. Once injected, the drug is absorbed by macrophages already present at the tumor site.
The drug contains genetic instructions that cause these macrophages to produce special proteins known as CAR proteins. CAR stands for chimeric antigen receptor, which allows immune cells to recognize and attack cancer cells.
When macrophages begin producing these CAR proteins, they are transformed into what scientists call CAR-macrophages.
These modified macrophages gain the ability to recognize cancer cells more effectively and actively destroy them. Because this transformation happens inside the body, it avoids many of the difficulties associated with current immune cell therapies.
Treating solid tumors has always been a major challenge. These tumors form tight physical barriers that block immune cells from entering. They also release signals that suppress immune activity. Traditional CAR-based therapies often rely on immune cells called T cells, which struggle to enter solid tumors and remain active once inside.
Macrophages, however, have unique advantages. They can move through dense tissue, directly engulf cancer cells, and send signals that activate other immune cells nearby. This makes them especially promising for treating solid tumors.
Until now, CAR-macrophage therapies required doctors to remove immune cells from a patient, modify them in specialized laboratories, and then return them to the body. This process is slow, expensive, and complex, making it difficult to use widely.
The KAIST team’s new approach avoids all of these steps. They used tiny particles called lipid nanoparticles that are designed to be easily taken up by macrophages. These particles carry two key components.
One is messenger RNA that gives macrophages instructions to produce CAR proteins. The other is a substance that activates immune signaling and strengthens the macrophages’ cancer-fighting behavior.
Once injected into a tumor, macrophages quickly absorb these nanoparticles. Inside the cells, the genetic instructions are used to produce CAR proteins, while immune activation signals help overcome the suppressive tumor environment. The result is a new type of enhanced CAR-macrophage created directly inside the body.
In animal studies using melanoma, one of the most aggressive forms of skin cancer, this treatment showed strong results. Tumor growth was greatly reduced after treatment. The modified macrophages not only attacked cancer cells directly but also stimulated other immune cells around them, creating a stronger and more coordinated immune response.
Researchers also observed signs that the immune response extended beyond the treated tumor. This suggests that the therapy could help the immune system recognize and fight cancer in other areas of the body as well, offering the possibility of broader protection.
Professor Ji-Ho Park explained that this study introduces a completely new way of thinking about immune cell therapy.
By generating cancer-fighting immune cells directly inside the patient’s body, the approach overcomes major limitations of existing treatments. It improves delivery efficiency and helps immune cells function even in the highly suppressive tumor environment.
While more research and human clinical trials are needed, this breakthrough opens a promising new direction for cancer immunotherapy. It suggests that future treatments may not require complex cell extraction procedures, but instead rely on activating the body’s own immune cells exactly where they are needed most.
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