CAR-T cell engineered with TCR-like antibody specific for HBV surface antigen epitope E183–91/HLA-A *0201 exhibit potent activity against HBV-HCC

作者：Fengling Wang, Jiaqian Li, Yong Huang, Feiyang Yan, Haozhan Gao, Weilin Zhou, Xinyu Gu, Dan Li, Yalan Zhang, Jing Li, Yuening Yang, Jianping Yang, Mengxi Zhang, Jinrong Yang, Shanhua Qi, Wei Wang · 发表于：OncoImmunology · 年份：2025 · DOI：10.1080/2162402x.2025.2546404 · 被引用次数：4 · 研究领域：CAR-T cell therapy research、Immunotherapy and Immune Responses、Virus-based gene therapy research

CAR-T cell therapy demonstrates significant efficacy in hematologic malignancies, with target selection critically determining therapeutic outcomes. However, the available tumor surface antigens are limited, especially in the treatment of solid tumors. A potential solution to overcome this limitation entails employing antibodies recognizing peptide-major histocompatibility complex (pMHC) structures, enabling CAR-T cell to detect intracellular tumor antigens through a T cell receptor (TCR)-like recognition mechanism. This study focuses on HBV-associated hepatocellular carcinoma (HBV-HCC), where HBV DNA integration into the host genome generates specific viral antigen epitopes presented by MHC class I molecules, representing attractive targets for CAR-T cell therapy. We engineered CAR-T cells with a TCR-like antibody (HBs183 CAR-T) specific for the immunodominant HBV envelope epitope Env183-191 presented by HLA-A *0201, and evaluated the antigen-specific cytotoxicity and safety profile of the CAR-T cells through in vitro functional assays and in vivo evaluation in heterogenous tumor models (subcutaneous and intraperitoneal xenografts). Our research provides a reference for CAR-T cell therapy targeting intracellular antigens, particularly specific antigens derived from viral infections, as targets for CAR-T treatment, and offers a preliminary concept validation for the CAR-T treatment of HBV-HCC tumors.