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Peer-reviewedCC BYFrontiers in immunology

Dendritic-cell-targeting adeno-associated virus as potent cancer vaccine carriers

  • Xin Wei1
  • Xiang Li2
  • Lixia Qi2
  • Wenxuan Qiu1
  • Yuxin Zhang1
  • Liping Wu1
  • Shutang Wei1
  • Bofeng Luo1
  • Menghan Shi1
  • Chenhao Liu1
  • Qi Yang1
  • Wenyi Yang1
1 more authors
  • Dengke Bao1
  1. 1The Department of Gastroenterology, The First Affiliated Hospital of Henan University , , ,
  2. 2Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University , , ,
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Abstract

Background: The clinical efficacy of therapeutic cancer vaccines is critically limited by the inefficient in vivo delivery of tumor antigens to dendritic cells (DCs), the key regulators of T-cell immunity.

Methods: To address this issue, we developed a dendritic-cell-targeting adeno-associated virus (AAV) vector through rational capsid design. This was achieved by site-specifically inserting the high-affinity Clec9a-targeting peptide CBP-12, optimizing its flanking sequences, and introducing T491V/S662V gain-of-function mutations to synergistically enhance DC transduction.

Results: The resulting vector, AAV2-mut-Peptide2, showed significantly improved tropism for and gene delivery efficiency to cross-presenting cDC1s in vivo . In murine models of hepatocellular carcinoma, vaccination with this platform, encoding either a model antigen (OVA) or the endogenous tumor-associated antigen GPC3, elicited a potent antigen-specific CD8+ T cell response. This response was characterized by a substantial increase in tumor-infiltrating lymphocytes, enhanced production of key effector cytokines, and consequently, potent suppression of tumor growth.

Conclusion: Our study establishes this engineered AAV as a versatile and potent vaccine platform that effectively targets DCs, offering a promising approach for inducing robust and adaptable anti-tumor immunity.

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Cite

BibTeXRIS
BibTeX
@article{wei2026dendriticcelltargeting,
  title = {{Dendritic-cell-targeting adeno-associated virus as potent cancer vaccine carriers}},
  author = {Xin Wei and Xiang Li and Lixia Qi and Wenxuan Qiu and Yuxin Zhang and Liping Wu and Shutang Wei and Bofeng Luo and Menghan Shi and Chenhao Liu and Qi Yang and Wenyi Yang and Dengke Bao},
  journal = {Frontiers in immunology},
  year = {2026},
  month = sep,
  doi = {10.3389/fimmu.2026.1932907},
  url = {https://europepmc.org/article/PMC/PMC13662115},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Dendritic-cell-targeting adeno-associated virus as potent cancer vaccine carriers
AU  - Xin Wei
AU  - Xiang Li
AU  - Lixia Qi
AU  - Wenxuan Qiu
AU  - Yuxin Zhang
AU  - Liping Wu
AU  - Shutang Wei
AU  - Bofeng Luo
AU  - Menghan Shi
AU  - Chenhao Liu
AU  - Qi Yang
AU  - Wenyi Yang
AU  - Dengke Bao
PY  - 2026
DA  - 2026/09/30
JO  - Frontiers in immunology
DO  - 10.3389/fimmu.2026.1932907
UR  - https://europepmc.org/article/PMC/PMC13662115
AB  - Background: The clinical efficacy of therapeutic cancer vaccines is critically limited by the inefficient in vivo delivery of tumor antigens to dendritic cells (DCs), the key regulators of T-cell immunity.  Methods: To address this issue, we developed a dendritic-cell-targeting adeno-associated virus (AAV) vector through rational capsid design. This was achieved by site-specifically inserting the high-affinity Clec9a-targeting peptide CBP-12, optimizing its flanking sequences, and introducing T491V/S662V gain-of-function mutations to synergistically enhance DC transduction.  Results: The resulting vector, AAV2-mut-Peptide2, showed significantly improved tropism for and gene delivery efficiency to cross-presenting cDC1s in vivo . In murine models of hepatocellular carcinoma, vaccination with this platform, encoding either a model antigen (OVA) or the endogenous tumor-associated antigen GPC3, elicited a potent antigen-specific CD8+ T cell response. This response was characterized by a substantial increase in tumor-infiltrating lymphocytes, enhanced production of key effector cytokines, and consequently, potent suppression of tumor growth.  Conclusion: Our study establishes this engineered AAV as a versatile and potent vaccine platform that effectively targets DCs, offering a promising approach for inducing robust and adaptable anti-tumor immunity.
SN  - 1664-3224
ER  -