Bispecific antibody engineered extracellular vesicles redirect T cells to prevent postoperative epidural fibrosis
Epidural fibrosis (EF) is a frequent and debilitating complication that impairs recovery following spinal surgery, yet effective targeted therapies are lacking. Here we observe enrichment of FAP⁺ fibroblasts at surgical sites in patients after laminectomy. To therapeutically target this subset, we develop bispecific antibody-decorated extracellular vesicles (BsAb EVs), which redirect endogenous T cells to eliminate FAP⁺ fibroblasts in situ. In a preclinical model, BsAb EVs selectively eliminate pathogenic fibroblasts, reduce fibrotic collagen accumulation, and prevent the development of postoperative epidural fibrosis without detectable systemic toxicity under the tested conditions. Single-cell RNA sequencing reveals that FAP⁺ fibroblasts represent a transcriptionally distinct subset from α-SMA⁺ myofibroblasts, characterized by enhanced extracellular matrix remodeling and TGF-β production. Together, these findings highlight a critical stromal subset in EF pathogenesis and position BsAb EVs as a promising immunotherapeutic strategy for targeting pathogenic stromal cells in fibrotic and tissue-remodeling disorders.
Authors
- Vijay Bhoj (ORCID: https://orcid.org/0000-0003-2857-4092)
- Ellen Puré (ORCID: https://orcid.org/0000-0003-2107-3711)
- Hui Lü (ORCID: https://orcid.org/0000-0003-2336-2170)
- Lugui Qiu (ORCID: https://orcid.org/0000-0002-8752-0644)
- Yan Xu (ORCID: https://orcid.org/0000-0002-3319-4695)
- Y Li (ORCID: https://orcid.org/0000-0002-1282-5312)
- Shanwei Ye
- Qi Xu (ORCID: https://orcid.org/0000-0002-6512-0631)
- Liang Huang (ORCID: https://orcid.org/0000-0002-8370-3232)
- W H Wei
- Jianfeng Guo (ORCID: https://orcid.org/0000-0002-2893-912X)
- Xiaohua Zhu (ORCID: https://orcid.org/0000-0003-0495-9510)
- Zhenfeng Liu (ORCID: https://orcid.org/0000-0001-5502-9474)
- Zheng Zhang (ORCID: https://orcid.org/0000-0002-3242-5738)
- Feng Li (ORCID: https://orcid.org/0000-0001-5892-6496)
- DQ Zhu
- Zha Yang (ORCID: https://orcid.org/0009-0001-9265-5148)
- Jun Ran
- Wei Xiong
- Shiqi Gu
- Wei Wang
Institutions
- Tianjin University of Technology (CN)
- Institute of Hematology & Blood Diseases Hospital (CN)
- Tongji Hospital (CN)
- First Affiliated Hospital Zhejiang University (CN)
- Huazhong University of Science and Technology (CN)
- University of Pennsylvania (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-06-27
- DOI
- https://doi.org/10.1038/s41467-026-74883-3
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China