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. 2026 Mar 24.
doi: 10.1186/s12951-026-04166-y. Online ahead of print.

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

Shumin Luo  1   2 , Li Xiao  3 , Fang Xu  1   2 , Pengpeng Lu  1   2 , Yiyue Wang  1   2 , Chuanyun Li  4 , Enhong Xing  5 , Weihua Li  6   7
Affiliations
Free article

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

Shumin Luo et al. J Nanobiotechnology. .
Free article

Abstract

Background: 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 (DEXAGNP) that integrates liver cancer epitope presentation, innate immune activation, and checkpoint modulation. Human DEXAGNP was generated by loading HLA-A*02:01-restricted hAFP158-166 and hGPC3144-152 peptides, and murine DEXAGNP by loading mAFP212-219 and mGPC3127-136 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.

Results: DEXAGNP vaccine enhanced antigen-specific CD8⁺ T-cell responses, as supported by peptide-MHC tetramer staining, and promoted cytokine-associated effector activity. In vitro, DEXAGNP-primed T cells mediated cytotoxicity against both human and murine liver cancer cell lines. In vivo, DEXAGNP 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, DEXAGNP 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.

Conclusion: DEXAGNP 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.

Keywords: Cancer vaccine; Dendritic cell-derived exosomes; Epitope peptides; Immunotherapy; Liver cancer; PD-L1 blockade.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This research was conducted in accordance with international guidelines and the ethical standards outlined in the Declaration of Helsinki. This study was approved by the Medical Ethics Committee of Capital Medical University (AEEI-2023–151), and written informed consent was obtained from each patient for the use of their tissue/PBMC samples. All animal experiments were conducted in compliance with the institutional guidelines of the Animal Experiment Center of the University/Animal Biosafety Level-III laboratory for the Use of Animals. All animal procedures were approved by the Experimental Animal Welfare Ethics Committee of Capital Medical University. Competing interests: The authors declare no competing interests.

References

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