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Antibody Generation Using Cancer-Derived Small Extracellular Vesicles (sEVs): A Platform for Targeted Cancer Therapy

Maryam Firouzi1, Changsun Kang1, Xiaoyu Ren1

  • 1Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Campus, Oklahoma City, OK, 73117, USA.

Small (Weinheim an Der Bergstrasse, Germany)
|November 28, 2025
PubMed
Summary

Researchers developed a new method using cancer-derived extracellular vesicles to create targeted antibodies for ovarian cancer therapy. This approach enhances drug delivery and reduces tumor growth by activating the immune system.

Keywords:
CD8+ T cell sEVsmonoclonal antibodyovarian cancerpersonalized therapysmall extracellular vesiclestargeted drug delivery

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In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
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Area of Science:

  • Oncology
  • Immunology
  • Nanotechnology

Background:

  • Drug delivery to solid tumors faces challenges, limiting the efficacy of targeted therapies.
  • Effective targeting ligands are crucial for improving preclinical and clinical cancer treatment outcomes.
  • Small extracellular vesicles (sEVs) can inherit features from parent cancer cells, offering potential for drug delivery.

Purpose of the Study:

  • To develop a novel method for generating tumor-targeting monoclonal antibodies (mAbs) using cancer-derived small extracellular vesicles (sEVs).
  • To evaluate the efficacy of antibody-functionalized sEVs loaded with paclitaxel in reducing ovarian carcinoma tumor growth.
  • To investigate the biodistribution and immune-modulating effects of these targeted sEVs.

Main Methods:

  • Generating mAbs by immunizing mice with ovarian cancer cell-derived sEVs and employing hybridoma technology.
  • Decorating paclitaxel-loaded CD8+ T cell-derived sEVs (TSEV/P) with selected mAbs to create antibody-functionalized TSEV/P (AB-TSEV/P).
  • Assessing tumor growth, body weight, biodistribution (using IR780 labeling), RNA sequencing, and spatial transcriptomics in OVCAR-8 tumor-bearing mice.

Main Results:

  • Both AB-TSEV/P formulations significantly inhibited tumor growth in OVCAR-8 bearing mice without causing weight loss.
  • Biodistribution studies showed enhanced accumulation of antibody-decorated sEVs in tumors compared to non-targeted controls.
  • Transcriptomic analysis revealed that antibody-decorated sEVs induced immune activation and tumor suppression signatures.

Conclusions:

  • The novel antibody generation strategy utilizing cancer-derived sEVs enables specific cancer cell targeting.
  • Antibody-functionalized sEVs demonstrate potential as an effective platform for targeted cancer therapy.
  • This approach supports applications in personalized oncology and advanced targeted cancer treatments.