研究人员设计了乙型肝炎病毒特异性T细胞，一种在体内发现

StephenW

Researchers have engineered hepatitis B virus-specific T cells, a type of immune cell found in the body, to treat hepatocellular carcinoma, a commonly occurring liver cancer.

The researchers also individualized the treatment, making the T cells specific to the patients. The team successfully performed the approach on two liver transplanted patients who had hepatitis B virus (HBV) associated liver cancer recurrence, with one patient seeing a reduction in size of the tumor lesions.

Chronic HBV infection is predominant in Asia and is highly associated with the development of hepatocellular carcinoma (HCC), a commonly occurring liver cancer. The current effective treatments for small to moderate size HCC include only surgery, liver transplantation, and loco-regional treatment that kill cancer cells by interventional radiologic means. Treatment with drugs only leads to a modest increase in the overall survival in more extensive disease. In patients who have HCC recurrence after liver transplantation, the treatment options are even more limited.

“In this study we showed that the integrated HBV-DNA gene components in the HCC cells were able to activate functional HBV-specific T cells,” says senior coauthor Antonio Bertoletti, a professor from the emerging infectious diseases program at Duke-NUS.

“Hence, by analyzing the specific HBV-DNA integration patterns in these HCC cells, we were able to select, design, and engineer the individualized T cells for therapy. Our studies showed that these engineered T cells were able to destroy the tumor.

“There were over 20 T cell infusions that were successfully performed on the two liver- transplanted patients,” says coauthor Thinesh Lee Krishnamoorthy, a consultant in the gastroenterology and hepatology department at Singapore General Hospital. “None of the patients experienced adverse reactions related to the treatment and one of them had a reduction in the tumor size of distant metastases of the liver cancer.

“Given that 80 percent of the HCC cases in Asia are currently HBV-related, this approach could lead to a major breakthrough in improving the survival and quality of life of patients suffering from this disease.”

The authors plan to further refine the technique and treatment strategy with further research and trials to improve the efficacy of the therapy.

Additional researchers who contributed to the work came from Duke-NUS; SGH; and Singapore biotech company Lion TCR.

Source: Duke-NUS

Original Study DOI: 10.1053/j.gastro.2019.01.251

StephenW

研究人员设计了乙型肝炎病毒特异性T细胞，一种在体内发现的免疫细胞，用于治疗肝细胞癌，这是一种常见的肝癌。

研究人员还对治疗进行了个体化，使T细胞对患者具有特异性。该团队成功地对两名肝移植患者进行了该方法，这些患者患有乙型肝炎病毒（HBV）相关的肝癌复发，其中一名患者看到肿瘤病灶大小减少。

慢性HBV感染在亚洲占主导地位，并且与肝细胞癌（HCC）（一种常见的肝癌）的发展密切相关。目前对中小型HCC的有效治疗仅包括手术，肝移植和通过介入放射学手段杀死癌细胞的局部区域治疗。用药物治疗仅导致更广泛疾病的总体存活率适度增加。在肝移植后发生HCC复发的患者中，治疗选择更加有限。

“在这项研究中，我们发现HCC细胞中整合的HBV-DNA基因成分能够激活功能性HBV特异性T细胞，”Duke-NUS新兴传染病项目教授，高级合着者Antonio Bertoletti说。

“因此，通过分析这些HCC细胞中特定的HBV-DNA整合模式，我们能够选择，设计和设计个体化T细胞进行治疗。我们的研究表明，这些工程化的T细胞能够破坏肿瘤。

“在两名肝移植患者中成功进行了20多次T细胞输注，”共同作者Thinesh Lee Krishnamoorthy说，他是新加坡中央医院胃肠病学和肝病学系的顾问。 “没有患者出现与治疗相关的不良反应，其中一例患者的肝癌远处转移瘤的肿瘤大小减少。

“鉴于亚洲80％的HCC病例目前与HBV有关，这种方法可能会在改善患此病的患者的生存和生活质量方面取得重大突破。”

作者计划通过进一步的研究和试验进一步完善技术和治疗策略，以提高治疗效果。

为这项工作做出贡献的其他研究人员来自Duke-NUS; SGH;和新加坡生物技术公司Lion TCR。

资料来源：Duke-NUS

原始研究DOI：10.1053 / j.gastro.2019.01.251