A KIF20A-based thermosensitive hydrogel vaccine effectively potentiates immune checkpoint blockade therapy for hepatocellular carcinoma.

Abstract

Hepatocellular carcinoma (HCC) is a highly prevalent malignancy with limited treatment efficacy despite advances in immune checkpoint blockade (ICB) therapy. The inherently weak immune responses in HCC necessitate novel strategies to improve anti-tumor immunity and synergize with ICB therapy. Kinesin family member 20A (KIF20A) is a tumor-associated antigen (TAA) overexpressed in HCC, and it could be a promising target for vaccine development. This study confirmed KIF20A as a promising immunogenic antigen through transcriptomic mRNA sequencing analysis in the context of HCC. Therefore, we developed a thermosensitive hydrogel vaccine formulation (K/R^Lip@Gel) to optimize antigen delivery while enabling sustained in vivo release. The vaccine efficiently elicited robust immune responses by activating DCs and T cells. Moreover, K/R^Lip@Gel improved the therapeutic efficacy of PD-L1 blockade in subcutaneous and orthotopic cell-derived xenograft (CDX) models, along with immune-humanized patient-derived xenograft (PDX) HCC models, which was evidenced by improved maturation of DCs and elevated infiltration and activation of CD8⁺ T cells. These findings highlight the potential of KIF20A-based vaccines to synergistically improve ICB therapy outcomes in HCC, providing a promising approach for enhancing anti-tumor immunity and improving clinical outcomes.