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<p>It is challenging for cancer vaccines to identify immunogenic antigens that are specifically and uniformly expressed on heterogeneous solid tumours and that can elicit production of T cells to lyse antigen-positive tumour cells and expand within the immunosuppressive tumour microenvironment. In contrast, microbial antigens are well-defined and robustly immunogenic and can activate specific memory T cells to eliminate microbes within the tumour microenvironment. Inspired by this, we developed a hepatitis B surface antigen (HBsAg)-tagged tumour vaccine system (H-T<sub>VAC</sub>). H-T<sub>VAC</sub> leverages HBsAg-specific memory T cells from a HBsAg mRNA vaccine to target and lyse HBsAg-tagged tumour cells using the vaccinia virus. This approach also elicits a tumour-specific immune response through epitope spreading by recruiting dendritic cells, thereby eliminating heterogeneous solid tumours. In various preclinical murine models, including the B16-OVA, B16F10, MC38, CT26, 4T1 and H22 hepatocellular carcinoma, as well as a B16F10 bilateral tumour model, H-T<sub>VAC</sub> demonstrates anti-tumour immune responses, improved survival rates and reduced metastasis and recurrence.</p>

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HBsAg-tagged tumour vaccine system eliminates solid tumours through virus-specific memory T cells

  • 期刊论文

  • 发表日期：

    2025年11月17日

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  • Wenguang Wang,
  • Ya Chu,
  • Lili Zhao,
  • Miao Lv,
  • Luyao Wang,
  • Fangfei Jin,
  • Kaiyuan Hu,
  • Lihang Cen,
  • Shuang Qin,
  • Xianjing Li,
  • Weijun Zhao,
  • Yiqiao Hu,
  • Shuguang Zuo,
  • Yong Yang

摘要

It is challenging for cancer vaccines to identify immunogenic antigens that are specifically and uniformly expressed on heterogeneous solid tumours and that can elicit production of T cells to lyse antigen-positive tumour cells and expand within the immunosuppressive tumour microenvironment. In contrast, microbial antigens are well-defined and robustly immunogenic and can activate specific memory T cells to eliminate microbes within the tumour microenvironment. Inspired by this, we developed a hepatitis B surface antigen (HBsAg)-tagged tumour vaccine system (H-TVAC). H-TVAC leverages HBsAg-specific memory T cells from a HBsAg mRNA vaccine to target and lyse HBsAg-tagged tumour cells using the vaccinia virus. This approach also elicits a tumour-specific immune response through epitope spreading by recruiting dendritic cells, thereby eliminating heterogeneous solid tumours. In various preclinical murine models, including the B16-OVA, B16F10, MC38, CT26, 4T1 and H22 hepatocellular carcinoma, as well as a B16F10 bilateral tumour model, H-TVAC demonstrates anti-tumour immune responses, improved survival rates and reduced metastasis and recurrence.