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Patient-Specific "Blood–Brain Tumor Barrier Chip" Predicts How Glioblastoma Patients Will Respond to Treatment
Even for the same brain tumor treated with the same anticancer drug, the effect can differ from patient to patient. A Korean research team has developed a chip that recreates a patient's own tumor cells together with the surrounding peritumoral vascular environment, making it possible to predict patient-specific treatment responses in advance.
KAIST (President Choongsik Bae) announced on August 18 that a research team led by Professor Song Ih Ahn from the Department of Mechanical Engineering, in collaboration with Professor Jungho Ahn's team at Sungkyunkwan University, Professor Jaejoon Lim of CHA Bundang Medical Center, and Professor Youn-Jung Kang's team at CHA University, has developed a patient-specific blood–brain tumor barrier (BBTB) chip capable of predicting treatment responses in glioblastoma patients.
Glioblastoma is one of the most lethal malignant brain tumors, hard to treat because the cancer cells spread rapidly into normal brain tissue and tumor characteristics differ from patient to patient. The brain is also protected by a "blood–brain barrier," which blocks harmful substances in the blood from entering brain tissue. The problem is that it blocks anticancer drugs too, so not enough of the drug reaches the tumor. When glioblastoma develops, this vascular barrier changes as well. How much it changes differs from patient to patient, which is one reason the same drug can work differently in different people.
Predictions of treatment response have so far relied mainly on tumor genetic information and biomarkers, which cannot capture the patient-specific vascular environment around the tumor or the resulting drug response.
To address this, the team built a chip that includes not only the patient's tumor cells but also the vascular barrier. This barrier is the "route" an anticancer drug must travel to reach the tumor. Patient-derived glioblastoma cells were co-cultured with brain vascular endothelial cells and astrocytes inside a small microfluidic chip. Together they recreate the boundary where tumor tissue meets normal brain tissue. The design also accommodates perivascular and immune cells, allowing the tumor's vascular environment to be reproduced more precisely.
Using tumor cells from three glioblastoma patients, the team built patient-mimicking BBTB chips and applied temozolomide (TMZ) and bevacizumab (BEV), the standard agents in glioblastoma treatment, to compare responses.
The three patients showed the same result on conventional genetic testing, the MGMT promoter methylation biomarker, and were therefore expected to respond similarly. On the chip, however, both the vascular barrier characteristics and the drug responses differed from one patient to another. The chip results showed a high level of agreement with the patients' actual clinical courses, indicating that outcomes can vary with the state of the vascular barrier even when genetic information is similar.
The core advance is that the platform evaluates not only whether cancer cells respond to a drug, but how a treatment acts within a given patient's tumor environment. If predictive performance and reproducibility are validated in a larger cohort, several agents could be tested on a chip made from a patient's own tumor cells to select the most promising strategy in advance. The same environment could also serve to screen new drug candidates.
Professor Song Ih Ahn said, "This study is meaningful in that it presents a platform that recreates patient-derived tumor cells together with the blood–brain tumor barrier, allowing patient-to-patient differences in treatment response to be evaluated in a way that closely reflects reality," adding, "We hope to validate it in a larger patient population and develop it into a preclinical evaluation platform for establishing personalized treatment strategies and for new drug development."
Minsu Ryoo, a doctoral student in KAIST's Department of Mechanical Engineering, and Gaeun Lee, a doctoral student at Sungkyunkwan University, participated as co-first authors. The results were published on June 27, 2026, in Small, an international journal in materials and nanoscience, and were selected as the journal's Front Cover.
Paper title: Human Blood-Brain Tumor Barrier on a Chip to Investigate Personalized Treatment for Glioblastoma Patients
DOI: 10.1002/smll.202506712
This research was supported by the Korea–US Collaborative Research Fund of the Ministry of Health and Welfare and the Korea Health Industry Development Institute (RS-2024-00468873), and by the Early-Career Researcher Program of the Ministry of Science and ICT and the National Research Foundation of Korea (RS-2026-25487930).
2026.08.18 View 1217 -
KAIST Unveils New Possibilities for Treating Intractable Brain Tumors
< Photo 1. (From left) Professor Heung Kyu Lee, KAIST Department of Biological Sciences, and Dr. Keun Bon Ku >
Immunotherapy, which enhances the immune system's T cell response to eliminate cancer cells, has emerged as a key approach in cancer treatment. However, in the case of glioblastoma, an aggressive and treatment-resistant brain tumor, numerous clinical trials have failed to confirm their efficacy. Korean researchers have recently analyzed the mechanisms that cause T cell exhaustion, which is characterized by a loss of function or a weakened response following prolonged exposure to antigens in such intractable cancers, identifying key control factors in T cell activation and clarifying the mechanisms that enhance therapeutic effectiveness.
KAIST (represented by President Kwang Hyung Lee) announced on the 6th of November that Professor Heung Kyu Lee’s team from the Department of Biological Sciences, in collaboration with the Korea Research Institute of Chemical Technology (represented by President Young Kuk Lee), has confirmed improved survival rates in a glioblastoma mouse model. By removing the inhibitory Fc gamma receptor (FcγRIIB), the research team was able to restore the responsiveness of cytotoxic T cells to immune checkpoint inhibitors, leading to enhanced anticancer activity.
The research team examined the effect of FcγRIIB, an inhibitory receptor recently found in cytotoxic T cells, on tumor-infiltrating T cells and the therapeutic effectiveness of the anti-PD-1 immune checkpoint inhibitor.
< Figure 1. Study results on improved survival rate due to increased antitumor activity of anti-PD-1 treatment in inhibitory Fc gamma receptor(Fcgr2b) ablation mice with murine glioblastoma. >
Their findings showed that deleting FcγRIIB induced the increase of tumor antigen-specific memory T cells, which helps to suppress exhaustion, enhances stem-like qualities, and reactivates T cell-mediated antitumor immunity, particularly in response to anti-PD-1 treatment. Furthermore, FcγRIIB deletion led to an increase in antigen-specific memory T cells that maintained continuous infiltration into the tumor tissue.
This study presents a new therapeutic target for tumors unresponsive to immune checkpoint inhibitors and demonstrates that combining FcγRIIB inhibition with anti-PD-1 treatment can produce synergistic effects, potentially improving therapeutic outcomes for tumors like glioblastoma, which typically show resistance to anti-PD-1 therapy.
< Figure 2. Overview of the study on the enhanced response to anti-PD-1 therapy for glioblastoma brain tumors upon deletion of the inhibitory Fc gamma receptor (FcγRIIB) in tumor microenvironment. When the inhibitory Fc gamma receptor (FcγRIIB) of cytotoxic T cells is deleted, an increase in tumor-specific memory T cells (Ttsms) was observed. In addition, this T cell subset is identified as originating from the tumor-draining lymph nodes(TdLNs) and leads to persistent infiltration into the tumor tissue. Anti-PD-1 therapy leads to an increased anti-tumor immune response via Ttsms, which is confirmed by increased tumor cell toxicity and increased cell division and decreased cell de-migration indices. Ultimately, the increased cytotoxic T cell immune response leads to an increase in the survival rate of glioblastoma. >
Professor Heung Kyu Lee explained, "This study offers a way to overcome clinical failures in treating brain tumors with immune checkpoint therapy and opens possibilities for broader applications to other intractable cancers. It also highlights the potential of utilizing cytotoxic T cells for tumor cell therapy."
The study, led by Dr. Keun Bon Ku of KAIST (currently a senior researcher at the Korea Research Institute of Chemical Technology's Center for Infectious Disease Diagnosis and Prevention), along with Chae Won Kim, Yumin Kim, Byeong Hoon Kang, Jeongwoo La, In Kang, Won Hyung Park, Stephen Ahn, and Sung Ki Lee, was published online on October 26 in the Journal for ImmunoTherapy of Cancer, an international journal in tumor immunology and therapy from the Society for Immunotherapy of Cancer. (Paper title: “Inhibitory Fcγ receptor deletion enhances CD8 T cell stemness increasing anti-PD-1 therapy responsiveness against glioblastoma,” http://dx.doi.org/10.1136/jitc-2024-009449).
This research received support from the National Research Foundation of Korea, the Bio & Medical Technology Development Program, and the Samsung Science & Technology Foundation.
2024.11.15 View 13707 -
Two Professors Recognized for the National R&D Excellence 100
< Professor Haeng-Ki Lee (left) and Professor Jeong-Ho Lee (right) >
Two KAIST professors were listed among the 2019 National R&D Excellence 100 announced by the Ministry of Science and ICT and the Korea Institute of S&T Evaluation and Planning.
Professor Haeng-Ki Lee from the Department of Civil and Environmental Engineering was recognized in the field of mechanics and materials for his research on developing new construction materials through the convergence of nano- and biotechnologies.
In the field of life and marine science, Professor Jeong-Ho Lee from the Graduate School of Medical Science and Engineering was lauded for his research of diagnostic tools and therapies for glioblastoma and pediatric brain tumors.
A certificate from the Minister of Ministry of Science and ICT will be conferred to these two professors, and their names will be inscribed on a special 2019 National R&D Excellence 100 plaque to celebrate their achievements. The professors will also be given privileges during the process of new R&D project selection.
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2019.10.15 View 21300 -
Professor Jeong-Ho Lee Named the KAISTian of 2018
(Professor Jeong-Ho Lee (right) poses with President Sung-Chul Shin)
Professor Jeong-Ho Lee from the Graduate School of Medical Science and Engineering was selected as the KAISTian of the Year of 2018. The award was established in 2001 and recognizes the most outstanding scholars who have made significant research and scholastic achievements during the year. Professor Lee was awarded during the New Year ceremony held in the auditorium on January 2.
Professor Lee has investigated mutations arising in the brain for decades and has published in renowned journals such as Nature, Nature Medicine, and Cell. Last August, Professor Lee reported breakthrough research on glioblastoma in Nature, giving insight into understanding how the mutation causing glioblastoma starts and suggested novel ways to treat glioblastoma, which was thought to be incurable. (Click for more)
Professor Lee’s Translational Neurogenetics Laboratory lab is investigating innovative diagnostics and therapeutics for untreatable brain disorders including intractable epilepsy and glioblastoma. To commercialize his technology, he established the tech-startup SoVarGen and now works as its CTO.
Professor Lee credited all his lab colleagues and staff. “I know all of this research would not have possible without their sweat and effort. I am happy to receive this honorable award on behalf of them.”
Remembering the beginning of his career at KAIST in 2012, Professor Lee said “KAIST seemed to be a very high and formidable barrier for me, after completing my medical education in Korea. I thank my department professors and colleagues who led me to focus on the research path that I really wanted. They provided everything for my research environment to help make good results.”
“I will continue to strive for promoting the well-being of humanity by addressing various incurable diseases as well as developing novel therapeutics. That will be the way to promote the stature of KAIST at home and abroad,” he added.
2019.01.02 View 10091