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<p>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<sup>Lip</sup>@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<sup>Lip</sup>@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<sup>+</sup> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月3日

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  • Xingyang Zhao,
  • Feichao Xuan,
  • Zirong Li,
  • Xiangyi Yin,
  • Xiaojun Zeng,
  • Jiali Chen,
  • Chihua Fang

摘要

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/RLip@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/RLip@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.