2017年1月25日
|2023 年 9 月 20 日|新闻稿
新闻稿
Antonio Bertoletti博士和其研究团队与伦敦大学学院、意大利比萨大学医院以及伦敦国王学院的研究团队合作，对一名HBV相关肝细胞癌患者进行了T细胞免疫治疗。 这项最初的临床试验展示了“针对肝细胞癌的自体TCR重定向疗法的可行性”，证实了TCR-T细胞疗法在临床应用中针对其他慢性病毒感染和相关并发症（例如癌症）的潜力。
摘要：
Abstract – HBV-DNA integration frequently occurs in HBV-related hepatocellular carcinoma (HCC), but whether HBV antigens are expressed in HCC cells and can be targeted by immune therapeutic strategies remains controversial. Here, we first characterized HBV antigen expression in HCC metastases, occurring in a patient who had undergone liver transplantation for HBV-related HCC. We then deployed for the first time in HCC autologous T cells, genetically modified to express an HBsAg specific T cell receptor, as therapy against chemoresistant extrahepatic metastases. We confirmed that HBV antigens were expressed in HCC metastases (but not in the donor liver) and demonstrated that tumour cells were recognized in vivo by lymphocytes, engineered to express an HBV-specific T cell receptor (TCR). Gene-modified T cells survived, expanded and mediated a reduction in HBsAg levels without exacerbation of liver inflammation or other toxicity. Whilst clinical efficacy was not established in this subject with end-stage metastatic disease, we confirm the feasibility of providing autologous TCR-redirected therapy against HCC and advocate this strategy as a novel therapeutic opportunity in hepatitis B-associated malignancies. PubMed
