Left) Schematic diagram of the research overview; Right) Photos and captions of Lee Sukmook and Shin Ha-kyung

A research team led by Professor Lee Sukmook of the Department of Biomedical Sciences at Kookmin University has developed a next-generation gene delivery platform that combines the team’s proprietary antibody engineering technology with virus-based gene delivery technology to enhance the expression of therapeutic proteins in cancer cells and induce an anti-cancer immune response. This study was led by Dr. Shin Ha-kyung, a postdoctoral researcher in the Department of Biomedical Sciences at Kookmin University, who served as the first author, and the findings were published in the international academic journal *International Journal of Biological Macromolecules* in November 2026.
 
Triple-negative breast cancer (TNBC) is a refractory form of breast cancer that is difficult to treat with conventional hormone therapy or HER2-targeted therapy; therefore, the development of new therapeutic targets and effective drug delivery technologies is considered a critical challenge. In particular, applying gene therapy technologies to cancer treatment requires techniques that effectively deliver therapeutic genes to cancer cells while minimizing off-target delivery to normal tissues.
 
To address these technical challenges, the research team utilized a large-scale nanobody library of approximately 71.6 billion entries—which they had independently constructed—to identify a nanobody (K118.1) that precisely recognizes the TROP2 protein, which is highly expressed in triple-negative breast cancer. K118.1 exhibited high binding affinity for both human and mouse TROP2 and demonstrated the ability to enter cells after binding to the target protein.
 
Subsequently, the research team developed a new gene delivery vector (rAAV-Nb) by applying capsid engineering—a technique that genetically inserts K118.1 into VP1, the capsid protein of recombinant adeno-associated virus (rAAV). This technology is designed to enhance gene delivery performance by incorporating the nanobody’s target recognition function into an existing viral vector, thereby leveraging its interaction with TROP2 on the surface of cancer cells.
 
Experimental results showed that the developed rAAV-Nb increased the expression level of the anticancer bispecific T-cell engager (BiTE) protein in triple-negative breast cancer cells by up to sixfold compared to conventional rAAV vectors. Furthermore, through competitive experiments using TROP2-expressing cells and soluble TROP2 protein, the team confirmed that the interaction between the nanobody and TROP2 contributes to improved gene delivery efficiency.
 
In particular, to verify whether the improved gene delivery efficiency leads to enhanced anticancer immune function, the research team loaded the gene for a bispecific T-cell engager (BiTE) that simultaneously recognizes CD155 on cancer cells and CD3 on T cells.
 As a result, experiments using human peripheral blood immune cells showed increased T-cell activation and cancer cell death; further experiments using primary human CD8-positive T cells also confirmed increased T-cell activation, elevated levels of anticancer-related effector molecules, and cancer cell death. These results demonstrate that the developed platform can enhance T-cell-mediated anticancer immune responses through the expression of functional anticancer proteins, going beyond a simple increase in gene expression. 
The greatest significance of this study lies in the fact that Kookmin University integrated its independently accumulated large-scale nanobody library and core antibody discovery technology with AAV gene delivery technology, linking this to the expression of functional anticancer proteins and immune cell-based anticancer effects. In particular, by conducting research that integrates antibody engineering and gene delivery technology—led by postdoctoral researcher Shin Ha-kyung—the study demonstrated the potential to expand the scope of application for the university’s proprietary antibody discovery technology to the development of next-generation gene and immunotherapy platforms.
 
Professor Lee Sukmook stated, “This study is highly significant in that the Kookmin University research team, based on its proprietary antibody engineering technology, has integrated cancer cell target recognition, therapeutic gene delivery, and anticancer immune responses into a single technological platform,” adding, “We plan to further develop this into a precision gene therapy platform tailored to specific cancer types by combining nanobodies that recognize various cancer cell surface proteins with therapeutic genes, and to systematically verify its anticancer efficacy and safety through subsequent preclinical studies,” he added.
 
This research represents a breakthrough in improving the functionality of gene delivery vectors using proprietary antibody engineering technology and applying it to anti-cancer immunotherapy. It is expected to serve as the foundation for the development of targeted gene delivery technologies and next-generation anti-cancer immunotherapies for various solid tumors in the future.