HBV 特异性 T 细胞可以靶向 HBV 相关肝细胞癌 (HBV-HCC) 中的 HBV-DNA 整合。 SCG101 是一种自体、HBV 特异性 T 细胞产物，在慢病毒转导后表达 T 细胞受体 (TCR)，识别 HLA-A2 上的包膜衍生肽 (S20-28)。我们在临床前验证了其安全性和有效性，并将其应用于 HBV 相关 HCC 患者 (NCT05339321)。对 GMP 级制造的细胞针对肝癌细胞的脱靶反应性和功能进行了评估。随后，一名晚期 HBV-HCC 患者（Child-Pugh：A、BCLC：B、ECOG：0、HBeAg-、血清 HBsAg、肝细胞 10% HBsAg）在淋巴细胞清除后接受 7.9x107 个细胞/kg。对安全性、T 细胞持久性以及抗病毒和抗肿瘤功效进行了评估。SCG101 在封闭袋系统中大量生产，在体外和体内均显示出针对 HBV 肝癌细胞的 HBV 特异性功能。临床上，治疗耐受性良好，所有不良事件（包括短暂性肝损伤）都是可逆的。第 3 天，ALT 水平增至 1404 U/ml，同时，血清 HBsAg 开始下降 3.84log，并在六个月内保持 <1 IU/ml。 73 天后，肝活检中检测不到表达 HBsAg 的肝细胞。根据 mRECIST 评分，患者实现了部分缓解，目标病灶尺寸缩小了 70% 以上。转移的 T 细胞扩增，形成干细胞样记忆表型，并且在患者血液中六个月后仍可检测到。SCG101 T 细胞疗法在临床前模型和原发性 HBV-HCC 患者中显示出令人鼓舞的疗效和安全性以及伴随的慢性乙型肝炎，单次给药后能够消除 HBsAg 细胞并实现持续的肿瘤控制。

HBV-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it in an HBV-related HCC patient (NCT05339321).GMP-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh:A, BCLC:B, ECOG:0, HBeAg-, serum HBsAg+, hepatocytes 10% HBsAg+) received 7.9x107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated.SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-hepatoma cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1404 U/ml, and concurrently, serum HBsAg started decreasing by 3.84log and remained <1 IU/ml for over six months. HBsAg expressing hepatocytes in liver biopsies were undetectable after73 days. The patient achieved a partial response according to mRECIST score with a >70% reduction of target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient's blood.SCG101 T-cell therapy showed encouraging efficacy and safety in pre-clinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.