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

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_VAC). H-T_VAC 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_VAC demonstrates anti-tumour immune responses, improved survival rates and reduced metastasis and recurrence.