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

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.