Recently, the research team led by Yang Yong and Wang Wenguang published a paper titled “HBsAg-tagged tumor vaccine system eliminates solid tumors through virus-specific memory T cells” in the top-tier journal Nature Biomedical Engineering. This study innovatively established a specific heterologous protein tagging system that “disguises” tumor cells as highly immunogenic “viruses.” This breakthrough addresses key bottlenecks long hindering tumor immunotherapy, including the low immunogenicity of tumor neoantigens, the strong heterogeneity of solid tumors, and the tumor-infiltrating immune-suppressive microenvironment (TIME). Associate Researcher Wang Wenguang from the School of Basic Medical Sciences and Clinical Pharmacy, along with 2024 doctoral candidate Chu Ya and 2025 doctoral candidates Zhao Lili and Lü Miao, served as co-first authors. Corresponding authors include Professor Yang Yong, Associate Researcher Wang Wenguang, Associate Researcher Zhao Weijun from our university, Associate Researcher Zuo Shuguang from Liuzhou Liutie Central Hospital, and Professor Hu Yiqiao from Nanjing University. China Pharmaceutical University is the first corresponding institution.
Tumor neoantigen vaccines offer a novel approach to precision cancer therapy by inducing tumor-specific immune responses. Currently, international vaccine giants like Moderna in the United States are focusing on utilizing tumor mutations to screen and design personalized neoantigen vaccines, with over 100 related clinical trials underway. However, due to the low immunogenicity of neoantigens (only about 15%–30% of neoantigens can induce T cell production), the high heterogeneity of solid tumors, and TIME suppression, the response rate of these personalized tumor neoantigen vaccines for solid tumors remains low. Addressing these critical challenges, Professor Yang Yong's team—specifically the Wang Wenguang laboratory—built upon nearly a decade of systematic research on oncolytic microorganisms (bacteria, viruses, etc.) (Nature Biomedical Engineering, 2022; Nature Communications, 2019; Journal of Controlled Release, 2025). They discovered that virus- or bacteria-specific memory T cells can maintain high effector function persistently within TIME and are less prone to exhaustion. Building upon this critical insight, the research team developed a universal tumor vaccine system specifically labeled with hepatitis B virus surface antigen (HBsAg-tagged tumor vaccine system, H-TVAC). This system “virus-like” modifies tumor cells to express highly immunogenic HBsAg, thereby mobilizing and redirecting long-standing HBV-specific memory T cells within the body. This enables precise tumor recognition and efficient lysis, further inducing epitope expansion and durable antitumor immune memory. In multiple immunologically “cold” tumor models including colorectal, breast, and liver cancers, H-TVAC demonstrated significant tumor clearance effects while effectively suppressing metastasis and recurrence, showcasing excellent clinical translation potential.
Compared to traditional personalized neoantigen vaccines based on sequencing-driven selection (which still suffer from low immunogenicity, lengthy preparation cycles, and high costs), the H-TVAC system offers distinct advantages: strong immunogenicity of heterologous proteins, well-defined antigenic epitopes, and the ability to leverage virus-specific memory T cells to overcome TIME (Figure 1). More importantly, this strategy eliminates the need for complex antigen prediction and screening processes, significantly reducing R&D and treatment costs while establishing a new paradigm for developing universal tumor vaccines. The research team is actively advancing the clinical translation of the H-TVAC system and invites PhD/Master's candidates and collaborative enterprises passionate about tumor vaccines and immunotherapy to join us in exploring new frontiers in cancer immunotherapy.
This research received support from multiple funding sources, including the National Natural Science Foundation of China (Youth Program and General Program), the Jiangsu Provincial Youth Fund, and Chen'an Bio's “Qingyun Plan.”
Figure 1. Schematic comparison of advantages between the universal tumor vaccine H-TVAC and tumor neoantigen vaccines
Full text link: https://www.nature.com/articles/s41551-025-01555-w
