Work

Immune-modified exosome vaccine loaded with liver cancer epitope peptides induces potent and specific antitumor immunity

Year: 2026

Type: article

Abstract: Dendritic cell-derived exosomes (DEXs) are emerging as effective platforms for cancer vaccines due to their capacity to present tumor antigens and regulate immune responses. Here, we developed a multifunctional DEX vaccine (DEX AGNP ) that integrates liver cancer epitope presentation, innate immune activation, and checkpoint modulation. Human DEX AGNP was generated by loading HLA-A*02:01-restricted hAFP 158-166 and hGPC3 144-152 peptides, and murine DEX AGNP by loading mAFP 212-219 and mGPC3 127-136 peptides. The N-terminal functional domain of high-mobility group nucleosome-binding protein 1 (N1ND) was membrane-anchored via CHOL-PEG2000, and programmed death ligand 1 (PD-L1) of DEXs surface was blocked with anti-PD-L1 antibodies to mitigate immunosuppression. DEX AGNP vaccine enhanced antigen-specific CD8⁺ T-cell responses, as supported by peptide-MHC tetramer staining, and promoted cytokine-associated effector activity. In vitro, DEX AGNP -primed T cells mediated cytotoxicity against both human and murine liver cancer cell lines. In vivo, DEX AGNP suppressed tumor growth in an immunocompetent subcutaneous H22 model and a humanized HepG2 xenograft model, and demonstrated antitumor activity in an orthotopic HCC model. In addition, DEX AGNP induced measurable killing in ex vivo assays using clinical HCC specimens and, in the prophylactic setting, was associated with enhanced memory-like T-cell responses. DEX AGNP is a modular exosome vaccine that combines epitope-specific antigen presentation with immune activation and PD-L1 blockade, enabling robust antitumor T-cell responses across complementary liver cancer models. This engineered DEX platform provides a practical blueprint for developing next-generation exosome-based cancer vaccines.

Source: Journal of Nanobiotechnology

DOI: 10.1186/s12951-026-04166-y

Authors: Shumin Luo, Li Xiao, Fang Xu, Pengpeng Lu, Yiyue Wang, Chuanyun Li, Enhong Xing, Weihua Li

Institutions: Capital Medical University, Beijing YouAn Hospital, Nanjing General Hospital of Nanjing Military Command, Nanjing University, Affiliated Hospital of Chengde Medical College

Language: English

Topic: Immunotherapy and Immune Responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,790