Dongin Kim

Antibody Generation Using Cancer‐Derived Small Extracellular Vesicles (sEVs): A Platform for Targeted Cancer Therapy and Potential Personalized Applications

Abstract Despite advances in tumor‐targeting therapies, drug delivery efficiency to solid tumors remains low in most preclinical studies, highlighting the need for more effective targeting ligands. A novel method is developed to generate tumor‐targeting monoclonal antibodies (mAbs) using cancer‐derived small extracellular vesicles (sEVs), which inherit the structural and functional features of their parent cells. sEVs isolated from human ovarian carcinoma cell lines (OVCAR‐8) are injected into mice to elicit an immune response. Hybridoma technology is used to generate mAbs, which are screened for either high specificity or cytotoxicity toward OVCAR‐8 cells. Two lead mAbs are individually decorated onto paclitaxel‐loaded CD8⁺ T cell‐derived sEVs (antibody‐functionalized TSEV/P; AB‐TSEV/P), and the resulting formulations are evaluated in OVCAR‐8 tumor‐bearing mice. Both AB‐TSEV/P formulations significantly reduce tumor growth without affecting body weight. Biodistribution studies using IR780‐loaded AB‐TSEV reveal enhanced tumor accumulation compared to non‐targeted controls. RNA sequencing and spatial transcriptomics show that antibody‐decorated sEVs induce transcriptional changes associated with immune activation and tumor suppression. This antibody generation strategy enables cancer cell‐specific targeting and supports its application in targeted cancer therapy and personalized oncology.

Understanding of Ovarian Cancer Cell-Derived Exosome Tropism for Future Therapeutic Applications

Exosomes, a subtype of extracellular vesicles, ranging from 50 to 200 nm in diameter, and mediate cell-to-cell communication in normal biological and pathological processes. Exosomes derived from tumors have multiple functions in cancer progression, resistance, and metastasis through cancer exosome-derived tropism. However, there is no quantitative information on cancer exosome-derived tropism. Such data would be highly beneficial to guide cancer therapy by inhibiting exosome release and/or uptake. Using two fluorescent protein (mKate2) transfected ovarian cancer cell lines (OVCA4 and OVCA8), cancer exosome tropism was quantified by measuring the released exosome from ovarian cancer cells and determining the uptake of exosomes into parental ovarian cancer cells, 3D spheroids, and tumors in tumor-bearing mice. The OVCA4 cells release 50 to 200 exosomes per cell, and the OVCA8 cells do 300 to 560 per cell. The uptake of exosomes by parental ovarian cancer cells is many-fold higher than by non-parental cells. In tumor-bearing mice, most exosomes are homing to the parent cancer rather than other tissues. We successfully quantified exosome release and uptake by the parent cancer cells, further proving the tropism of cancer cell-derived exosomes. The results implied that cancer exosome tropism could provide useful information for future cancer therapeutic applications.