Authors
Xin Wei, Xiang Li, Lixia Qi, Wenxuan Qiu, Yuxin Zhang, Liping Wu, Shutang Wei, Bofeng Luo, Menghan Shi, Chenhao Liu, Qi Yang, Wenyi Yang, Dengke Bao
Published in
Frontiers in immunology. Volume 17. Pages 1932907. Epub Sep 30, 2026.
Abstract
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.
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.
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.
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.
PMID:
42876800
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.
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