Abstract 4383: Utilization of HBV-vaccinated immunity to suppress tumor progression via targeted delivery of HBsAg to CEA-positive colorectal cancer

Abstract Limited antigen recognition hampers the anti-tumor efficacy of CD8+ T cells. We hypothesized that vaccinated immunity against hepatitis B virus (HBV) in individuals could be harnessed to target hepatitis B surface antigen (HBsAg)-expressed tumor cells, thereby suppressing tumor progression. We aimed to validate the proposed concept and to develop a tumor-targeting agent that delivers HBsAg to colorectal tumor cells via carcinoembryonic antigen (CEA)-targeted antibodies. We generated HBsAg-overexpressed CT26 colorectal tumor cells and utilized HBV-vaccinated BALB/c mice to evaluate the proposed concept. A fusion protein comprising a fragment of HBsAg (fHBs, amino acids 103-170) and a single-chain variable fragment (scFv) against CEACAM5 (CEA), linked to a Fc domain (fHBs-T84scFv-Fc), was constructed to deliver HBsAg into tumor cells for immune recognition and tumor suppression. We found that HBV-vaccinated mice exhibited strong anti-HBsAg responses and significantly suppressed HBsAg-overexpressed CT26 tumor growth, accompanied by increased CD3+ and CD8+ T cell infiltration in tumor tissues. CEACAM5 was identified as a colorectal tumor-specific receptor exhibiting internalization. We consequently demonstrated that the created anti-tumor reagent fHBs-T84scFv-Fc effectively bound tumor cells and inhibited growth of CEACAM5-positive MC38 tumors in the HBV-vaccinated mice. Meanwhile, enhanced infiltration of CD3+ and CD8+ T cells was observed in the tumor tissues under fHBs-T84scFv-Fc treatment. We demonstrated a novel strategy by utilizing HBV-vaccinated immunity for colorectal tumor suppression via CEA-targeted HBsAg delivery. This study suggests that the anti-HBV immunity containing anti-HBsAg CD8+ T cells can be utilized to suppress a range of tumors using HBsAg-antibody conjugates by targeting the tumor-specific internalizing receptors. Citation Format: Chun-Chia Cheng, Zong-Lin Sie, Yung-Chin Hsiao, Ai-Sheng Ho, Chih-Liang Wang, Cheng-Liang Peng, Chun-I Wang, Hong-Zen Yeh, Jungshan Chang, Chun-Chao Chang. Utilization of HBV-vaccinated immunity to suppress tumor progression via targeted delivery of HBsAg to CEA-positive colorectal cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4383.