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KAIST Awakens dormant immune cells inside tumors to attack cancer
<(From Left) Professor Ji-Ho Park, Dr. Jun-Hee Han from the Department of Bio and Brain Engineering>
Within tumors in the human body, there are immune cells (macrophages) capable of fighting cancer, but they have been unable to perform their roles properly due to suppression by the tumor. KAIST researchers have overcome this limitation by developing a new therapeutic approach that directly converts immune cells inside tumors into anticancer 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, when a drug is injected directly into a tumor, macrophages already present in the body absorb it, produce CAR (a cancer-recognizing device) proteins on their own, and are converted into anticancer immune cells known as “CAR-macrophages.”
Solid tumors—such as gastric, 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 attracted attention as a next-generation immunotherapy, have the advantage of directly engulfing cancer cells while simultaneously activating surrounding immune cells to amplify anticancer responses.
However, conventional CAR-macrophage therapies require immune cells to be extracted from a patient’s blood, followed by cell culture and genetic modification. This process is time-consuming, costly, and has limited feasibility for real-world patient applications.
To address this challenge, the research team focused on “tumor-associated macrophages” that are already accumulated around tumors.
They developed a strategy to directly reprogram immune cells in the body by loading lipid nanoparticles—designed to be readily absorbed by macrophages—with both mRNA encoding cancer-recognition information and an immunostimulant that activates immune responses.
In other words, in this study, CAR-macrophages were created by “directly converting the body’s own macrophages into anticancer cell therapies inside the body.”
<Figure . Schematic illustration of the strategy for in vivo CAR-macrophage generation and cancer cell eradication via co-delivery of CAR mRNA and immunostimulants using lipid nanoparticles (LNPs)>
When this therapeutic agent was injected into tumors, macrophages rapidly absorbed it and began producing proteins that recognize cancer cells, while immune signaling was simultaneously activated. As a result, the generated “enhanced CAR-macrophages” showed markedly improved cancer cell–killing ability and activated surrounding immune cells, producing a powerful 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 to induce systemic immune responses.
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,” 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.”
This research was led by Jun-Hee Han, Ph.D., of the Department of Bio and Brain Engineering at KAIST as the first author, and the results were published on November 18 in ACS Nano, an international journal in the field of nanotechnology.
※ Paper title: “In Situ Chimeric Antigen Receptor Macrophage Therapy via Co-Delivery of mRNA and Immunostimulant,” Authors: Jun-Hee Han (first author), Erinn Fagan, Kyunghwan Yeom, Ji-Ho Park (corresponding author), DOI: 10.1021/acsnano.5c09138
This research was supported by the Mid-Career Researcher Program of the National Research Foundation of Korea.
2025.12.31 View 2393 -
New Nanoparticle Drug Combination For Atherosclerosis
Physicochemical cargo-switching nanoparticles (CSNP) designed by KAIST can help significantly reduce cholesterol and macrophage foam cells in arteries, which are the two main triggers for atherosclerotic plaque and inflammation.
The CSNP-based combination drug delivery therapy was proved to exert cholesterol-lowering, anti-inflammatory, and anti-proliferative functions of two common medications for treating and preventing atherosclerosis that are cyclodextrin and statin. Professor Ji-Ho Park and Dr. Heegon Kim from KAIST’s Department of Bio and Brain Engineering said their study has shown great potential for future applications with reduced side effects.
Atherosclerosis is a chronic inflammatory vascular disease that is characterized by the accumulation of cholesterol and cholesterol-loaded macrophage foam cells in the intima. When this atherosclerotic plaque clogs and narrows the artery walls, they restrict blood flow and cause various cardiovascular conditions such as heart attacks and strokes. Heart attacks and strokes are the world’s first and fifth causes of death respectively.
Oral statin administration has been used in clinics as a standard care for atherosclerosis, which is prescribed to lower blood cholesterol and inhibit its accumulation within the plaque. Although statins can effectively prevent the progression of plaque growth, they have only shown modest efficacy in eliminating the already-established plaque. Therefore, patients are required to take statin drugs for the rest of their lives and will always carry the risk of plaque ruptures that can trigger a blood clot.
To address these issues, Professor Park and Dr. Kim exploited another antiatherogenic agent called cyclodextrin. In their paper published in the Journal of Controlled Release on March 10, Professor Park and Dr. Kim reported that the polymeric formulation of cyclodextrin with a diameter of approximately 10 nanometers(nm) can accumulate within the atherosclerotic plaque 14 times more and effectively reduce the plaque even at lower doses, compared to cyclodextrin in a non-polymer structure.
Moreover, although cyclodextrin is known to have a cytotoxic effect on hair cells in the cochlea, which can lead to hearing loss, cyclodextrin polymers developed by Professor Park’s research group exhibited a varying biodistribution profile and did not have this side effect.
In the follow-up study reported in ACS Nano on April 28, the researchers exploited both cyclodextrin and statin and form the cyclodextrin-statin self-assembly drug complex, based on previous findings that each drug can exert local anti-atherosclerosis effect within the plaque. The complex formation processes were optimized to obtain homogeneous and stable nanoparticles with a diameter of about 100 nm for systematic injection.
The therapeutic synergy of cyclodextrin and statin could reportedly enhance plaque-targeted drug delivery and anti-inflammation. Cyclodextrin led to the regression of cholesterol in the established plaque, and the statins were shown to inhibit the proliferation of macrophage foam cells. The study suggested that combination therapy is required to resolve the complex inflammatory cholesterol-rich microenvironment within the plaque.
Professor Park said, “While nanomedicine has been mainly developed for the treatment of cancers, our studies show that nanomedicine can also play a significant role in treating and preventing atherosclerosis, which causes various cardiovascular diseases that are the leading causes of death worldwide.”
This work was supported by KAIST and the National Research Foundation (NRF) of Korea.
Publications:
1. Heegon Kim, Junhee Han, and Ji-Ho Park. (2020) ‘Cyclodextrin polymer improves atherosclerosis therapy and reduces ototoxicity’ Journal of Controlled Release. Volume 319. Page 77-86. Available online at https://doi.org/10.1016/j.jconrel.2019.12.021
2. Kim, H., et al. (2020) ‘Affinity-Driven Design of Cargo-Switching Nanoparticles to Leverage a Cholesterol-Rich Microenvironment for Atherosclerosis Therapy’ ACS Nano. Available online at https://doi.org/10.1021/acsnano.9b08216
Profile: Ji-Ho Park, Ph.D.
Associate Professor
jihopark@kaist.ac.kr
http://openwetware.org/wiki/Park_Lab
Biomaterials Engineering Laboratory (BEL)
Department of Bio and Brain Engineering (BIOENG)
Korea Advanced Institute of Science and Technology (KAIST)
https://www.kaist.ac.kr
Daejeon 34141, Korea
Profile: Heegon Kim, Ph.D.
Postdoctoral Researcher
heegon@kaist.ac.kr
BEL, BIOENG, KAIST
(END)
2020.06.16 View 19651 -
Anti-Cancer Therapy Delivering Drug to an Entire Tumor Developed
KAIST’s Department of Bio and Brain Engineering Professor Ji-Ho Park and his team successfully developed a new highly efficacious anti-cancer nanotechnology by delivering anti-cancer drugs uniformly to an entire tumor. Their research results were published in Nano Letters online on March 31, 2015.
To treat inoperable tumors, anti-cancer medicine is commonly used. However, efficient drug delivery to tumor cells is often difficult, treating an entire tumor with drugs even more so.
Using the existing drug delivery systems, including nanotechnology, a drug can be delivered only to tumor cells near blood vessels, leaving cells at the heart of a tumor intact. Since most drugs are injected into the bloodstream, tumor recurrence post medication is frequent.
Therefore, the team used liposomes that can fuse to the cell membrane and enter the cell. Once inside liposomes the drug can travel into the bloodstream, enter tumor cells near blood vessels, where they are loaded to exosomes, which are naturally occurring nanoparticles in the body. Since exosomes can travel between cells, the drug can be delivered efficiently into inner cells of the tumor.
Exosomes, which are secreted by cells that exist in the tumor microenvironment, is known to have an important role in tumor progression and metastasis since they transfer biological materials between cells. The research team started the investigation recognizing the possibility of delivering the anti-cancer drug to the entire tumor using exosomes.
The team injected the light-sensitive anti-cancer drug using their new delivery technique into experimental mice. The researchers applied light to the tumor site to activate the anti-cancer treatment and analyzed a tissue sample. They observed the effects of the anti-cancer drug in the entire tumor tissue.
The team’s results establish a ground-breaking foothold in drug delivery technology development that can be tailored to specific diseases by understanding its microenvironment. The work paves the way to more effective drug delivery systems for many chronic diseases, including cancer tumors that were difficult to treat due to the inability to penetrate deep into the tissue.
The team is currently conducting experiments with other anti-cancer drugs, which are being developed by pharmaceutical companies, using their tumor-penetrating drug delivery nanotechnology, to identify its effects on malignant tumors.
Professor Park said, “This research is the first to apply biological nanoparticles, exosomes that are continuously secreted and can transfer materials to neighboring cells, to deliver drugs directly to the heart of tumor.”
Picture: Incorporation of hydrophilic and hydrophobic compounds into membrane vesicles by engineering the parental cells via synthetic liposomes.
2015.04.07 View 15153