https://scholar.dgist.ac.kr/handle/20.500.11750/8970 2026-09-13T08:28:41Z 2026-09-13T08:28:41Z Park, Jun-Kook Jung, Inseong Lee, Seunghyun Kim, Jisuk Shin, Sanghee Shin, Jiwon Noh, Soojeong Kwon, Dahye Nam, Chaerin Kim, Hyunwook Choi, Hongsoo Yea, Kyungmoo https://scholar.dgist.ac.kr/handle/20.500.11750/60676 2026-08-27T08:40:14Z 2026-06-30T15:00:00Z

Title: Engineering of tandem bispecific IL-7 receptor agonist antibody promoting selective T cell expansion Author(s): Park, Jun-Kook; Jung, Inseong; Lee, Seunghyun; Kim, Jisuk; Shin, Sanghee; Shin, Jiwon; Noh, Soojeong; Kwon, Dahye; Nam, Chaerin; Kim, Hyunwook; Choi, Hongsoo; Yea, Kyungmoo Abstract: Interleukin-7 (IL-7) is indispensable for T cell development and homeostasis, and clinical studies have demonstrated its ability to restore T cell numbers in lymphopenic conditions. However, the therapeutic application of IL-7 has been limited by its short half-life and potential immunogenicity of recombinant variants. To overcome these challenges, we engineered a fully human tandem bispecific antibody, TB4, that functions as a potent IL-7 receptor agonist by cis-targeting IL-7 receptor alpha (IL-7R alpha) and the common gamma chain (gamma c). The tetravalent tandem scFv-Fc architecture, coupled with optimized linker length, conferred markedly enhanced binding affinity and avidity compared to the knobs-into-holes bispecific format, with domain orientation designed to limit unintended gamma c binding. At the cellular level, TB4 engaged both receptor subunits and exhibited reduced internalization dynamics, features that are likely to contribute to the sustained STAT5 phosphorylation observed in primary human T cells. Functionally, TB4 supported long-term T cell survival and expansion, but selectively promoted the expansion of CD4+ memory subsets, especially effector memory cells re-expressing CD45RA populations, in contrast to the broader effects of native IL-7. Transcriptomic profiling further revealed that while both TB4 and IL-7 activated proliferative gene programs, TB4 uniquely drove an antiviral and innate immune signature. Collectively, these findings establish TB4 as a next-generation IL-7R agonist antibody with a differentiated mechanism of action and potential as a precision immunomodulator that can selectively expand and reprogram T cells.

2026-06-30T15:00:00Z Dutta, Sourav Patra, Tanushree Yea, Kyungmoo Choi, Hongsoo https://scholar.dgist.ac.kr/handle/20.500.11750/60217 2026-04-15T08:10:47Z 2026-01-31T15:00:00Z

Title: Magnetic hyperthermia-induced hydrogen therapy for cancer treatment using PEG-coated Mg–Ni Degradable microrobots Author(s): Dutta, Sourav; Patra, Tanushree; Yea, Kyungmoo; Choi, Hongsoo Abstract: Hydrogen therapy using magnesium-based micromotors offers a promising strategy for treating diseases such as cancer, diabetes, and Alzheimer’s, which are associated with elevated levels of reactive oxygen species (ROS). However, their clinical application is limited by uncontrollable motion and high reactivity in physiological environments. To overcome these challenges, we have developed a polymer-coated, magnetically guided magnesium (Mg) microrobot that integrates hydrogen therapy with magnetic hyperthermia. The polymer coating ensures stability in phosphate-buffered saline (PBS), while the microrobot achieves a velocity of 18.63 ± 0.85 μm/s under a 15 mT, 10 Hz rotating magnetic field. Mild magnetic heating (∼43 °C) partially melts the polymeric shell, triggering hydrogen release. In vitro studies with HCT 116 cells demonstrated a significant reduction in ROS at 3 mg/mL following magnetic hyperthermia. In vivo experiments in mice showed that the microrobot alleviated oxidative stress and significantly decreased tumor volume. These results indicated that Mg-based microrobots represent a controllable and effective therapeutic platform for ROS-related diseases. © 2026 .

2026-01-31T15:00:00Z Kim, Kiwook Jang, Juhee Cho, Juhyeong Ahn, Yongdeok Jeong, Seunghyeon Shin, Jiwon Yea, Kyungmoo Lee, Wonhee John Seo, Daeha https://scholar.dgist.ac.kr/handle/20.500.11750/59228 2025-11-27T08:10:10Z 2025-08-31T15:00:00Z

Title: Reconciling a Kinetic Model for Dimerization of the EGFR Using Single-Molecule Tracking in Living Cells Author(s): Kim, Kiwook; Jang, Juhee; Cho, Juhyeong; Ahn, Yongdeok; Jeong, Seunghyeon; Shin, Jiwon; Yea, Kyungmoo; Lee, Wonhee John; Seo, Daeha Abstract: Epidermal growth factor receptor (EGFR) dimerization plays a pivotal role in cellular signaling, influencing proliferation and disease progression, particularly in cancer. Despite extensive studies, the quantitative relationship between EGFR expression levels and dimerization efficiency remains incompletely understood. In this study, we investigated EGFR dimerization kinetics using ensemble-level biochemical assays and single-molecule tracking (SMT) in living cells. Our findings revealed noncanonical negative cooperative dimerization, where the monomer-to-dimer transition rate decreased as EGFR expression increased, challenging the assumptions of a simplistic reaction model. Furthermore, we identified a dimer-specific degradation pathway highlighting the open-system nature of the plasma membrane environment. These findings establish a quantitative framework for understanding EGFR dimerization dynamics, offering insights into the complex regulatory principles governing membrane protein interactions. This model not only improves our understanding of EGFR-mediated signaling but also suggests broader applicability for the therapeutic targeting of membrane protein systems.

2025-08-31T15:00:00Z Kang, Sung-Min Jung, Dokyung Noh, Soojeong Shin, Sanghee Kim, Minju Cho, Hanchae Lee, Byungheon Yea, Kyungmoo Baek, Moonchang https://scholar.dgist.ac.kr/handle/20.500.11750/59090 2026-02-03T10:40:22Z 2025-07-31T15:00:00Z

Title: Surface-Engineered Natural Killer Cell-Derived Small Extracellular Vesicles Induce Potent Anti-Tumour Effects in Lung Cancer Cells Author(s): Kang, Sung-Min; Jung, Dokyung; Noh, Soojeong; Shin, Sanghee; Kim, Minju; Cho, Hanchae; Lee, Byungheon; Yea, Kyungmoo; Baek, Moonchang Abstract: Small extracellular vesicles (sEVs) derived from natural killer (NK) cells possess inherent anti-tumour activity and offer the advantages of cell-free therapy. In this study, we genetically engineered NK-sEVs to express interleukin 15 (IL15), an anti-tumour cytokine, and the monoclonal antibody cetuximab on their surface, creating a potent anti-tumour immunotherapy with enhanced tumour-targeting capabilities. These IL15- and cetuximab-tethered NK-sEVs (eEVs) were generated using lentivirus-based modification. eEVs selectively bound to EGFR+ cancer cells in vitro, confirming cetuximab-mediated targeting. Compared to control NK-sEVs, eEVs exhibited significantly enhanced cytotoxicity by directly inducing cancer cell death and promoting NK cell-mediated killing. In a lung cancer mouse model, eEVs selectively accumulated in tumours and exhibited significant anti-tumour efficacy. Notably, their administration, alone or in combination with anti-PD-1 antibody therapy, effectively suppressed tumour growth. Overall, our results indicate that genetically engineered NK-sEVs, equipped with IL15 and cetuximab, exhibit potent anti-tumour activity and tumour-targeting capabilities. These findings suggest that eEVs hold significant potential as a novel immunotherapeutic strategy for cancer treatment. © 2025 Elsevier B.V., All rights reserved.

2025-07-31T15:00:00Z