Research Article: Dendritic-cell-targeting adeno-associated virus as potent cancer vaccine carriers
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.
Introduction:
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.
Read more