Clinical results of an HBV-specific T-cell receptor-T-cell therapy (SCG101) in patients with HBV-related hepatocellular carcinoma treated in an investigator-initiated, interventional trial

作者：Xiangan Wu, Dongmei Quan, Wei Li, Karin Wisskirchen, Wei Wu, Yuhong Zhou, Yunpeng Liu, Xueshuai Wan, Xiaorui Wang, Xuxu Zhang, Lu Yang, Mengyao Zheng, Ke Zhang, Ulrike Protzer, Shunda Du, Xiujuan Qu · 发表于：Gut · 年份：2025 · DOI：10.1136/gutjnl-2025-335456 · 被引用次数：14 · 研究领域：Hepatitis B Virus Studies、CAR-T cell therapy research、Cancer Immunotherapy and Biomarkers

Background SCG101 is an autologous T-cell therapy specifically targeting hepatitis B virus (HBV) using a natural, high-affinity T-cell receptor that is stably expressed. Objective We evaluated the safety, pharmacokinetics, pharmacodynamics and efficacy of SCG101 in patients with HBV-related hepatocellular carcinoma (HCC) in an investigator-initiated trial. Design Six human leucocyte antigen (HLA)-A*02:01-positive, serum hepatitis B surface antigen (HBsAg)-positive and hepatitis B e antigen-negative patients with advanced HBV-HCC, who had failed one to three prior systemic therapies, received SCG101 at doses of 5×10 7 or 1×10 8 TCR-T + cells/kg three days after lymphodepletion. Results Within 1 week, all patients experienced a significant but transient alanine aminotransferase elevation paralleled by a 76±57 fold expansion of T cells detected in peripheral blood. No neurotoxicity, but a cytokine release syndrome reaching up to grade 3 was observed. However, these side effects were not dose-limiting and could be managed with corticosteroids, anti-interleukin-6 and/or vasopressor therapy. Indicating on-target activity of SCG101, serum HBsAg levels dropped by 1.96 (0.16–3.84) log 10 within 2 weeks. According to modified Response Evaluation Criteria in Solid Tumours, three of the six patients achieved tumour shrinkage with a best percentage change in target lesion size of −19.5%, −74.6% and −100%. One showed complete remission of the target lesion, remaining progression-free for 2...