Checkmate 肝脏中的乙型肝炎病毒

StephenW

Checkmate for hepatitis B viruses in the liver28th August 2019
        
                                                                                
                        Researchers at Helmholtz Zentrum München and the Technical University of Munich, working in collaboration with researchers at the University Medical Center Hamburg-Eppendorf and the University Hospital Heidelberg, have for the first time succeeded in conquering a chronic infection with the hepatitis B virus in a mouse model. The team showed in its publication, that T-cell therapy can provide a permanent cure. Up to now it has not been possible to fully control the virus.
Infections with the hepatitis B virus (HBV) are a global health problem. According to the World Health Organisation (WHO), more than 260 million people worldwide are chronically infected with the virus. Vaccination prevents new HBV infections, but for people who are chronic carriers of the virus, a cure has not yet been found. Available drugs only prevent the virus from continuing to replicate in liver cells, but they cannot eliminate it. In the long term, this can lead to complications such as liver cancer or liver cirrhosis, whereby functional liver tissue is replaced by fibrous connective tissue.
"Currently, chronic hepatitis B cannot be cured. We have now been able to show that T-cell therapy exploiting new technologies presents an encouraging solution for the treatment of chronic HBV infection and liver cancer that is triggered by the virus. That is because these Œliving drugs¹ are the most potent therapy we have at our disposal at present," explains Prof. Ulrike Protzer. She is Director of the Institute of Virology at the Helmholtz Zentrum München and at the Technical University of Munich, both members of the German Center for Infection Research (DZIF).
T cells eliminate hepatitis BAccording to Dr. Karin Wisskirchen, first author of the study and scientist in the group of Ulrike Protzer, the new T-cell therapy was specifically developed as an approach to fighting HBV infection and HBV-associated liver cancer. It is known that in chronically infected patients, virus-specific T cells either cannot be detected or they demonstrate decreased activity. However, if patients are able to keep the virus under control by themselves, a strong T-cell response becomes detectable. "The obvious answer is therefore to use virus-specific T cells to make up for this deficit," Dr. Wisskirchen says. The genetic information for HBV-specific T-cell receptors was obtained from patients with resolved infection. In the laboratory, it can then be introduced into T cells from the blood of patients with chronic hepatitis B. This leads to the formation of new, active T cells, which fight the virus or virus-induced cancer cells. T cells created in this way were able to completely eliminate HBV-infected cells in the cell culture.
In cooperation with the group led by Prof. Maura Dandri, Hamburg the immune cells were then tested in a humanised mouse model. A single dose of the receptor-modified T-cells was sufficient to control the virus in the liver. Hereby, the T-cells only attacked infected liver cells and spared healthy tissue. Myrcludex B, an experimental drug developed by Prof. Stephan Urban, Heidelberg, was then administered to prevent the virus from infecting healthy liver cells again as soon as the T-cells had stopped circulating. As a result, the infection was completely cured.
Preparations for a clinical study"The promising results of this study will help us to further investigate the potential of T-cell therapy and go ahead with clinical trials along with our partners. We are thus taking a decisive step towards establishing this form of personalised medicine," Prof. Protzer says. Her group will therefore continue to explore ways of applying the therapy to the widest possible group of patients. The Helmholtz Zentrum München has out-licensed parts of its T-cell therapy to SCG Cell therapy Pte. Ltd. "Together with our partner we are planning a clinical trial to study the treatment of patients with HBV-associated hepatocellular carcinoma," Dr. Wisskirchen explains. T-cell therapy is a highly innovative area that has gained momentum thanks to the significant success of clinical trials in the treatment of lymphoma. Prof. Dandri stresses: "Such progress would not be possible without the close cooperation that we have within the German Center for Infection Research."



               
               

StephenW

检查肝脏中的乙型肝炎病毒
2019年8月28日

HelmholtzZentrumMünchen和慕尼黑技术大学的研究人员与汉堡 - 埃彭多夫大学医学中心和海德堡大学医院的研究人员合作，首次成功地克服了小鼠乙型肝炎病毒的慢性感染模型。该团队在其出版物中表明，T细胞疗法可以提供永久性治疗。到目前为止，尚无法完全控制病毒。

乙型肝炎病毒（HBV）感染是一个全球性的健康问题。据世界卫生组织（WHO）称，全球有超过2.6亿人长期感染该病毒。疫苗接种可预防新的HBV感染，但对于慢性携带病毒的人来说，还没有找到治愈方法。可用的药物只能阻止病毒在肝细胞中继续复制，但它们无法消除它。从长远来看，这可能导致肝癌或肝硬化等并发症，其中功能性肝组织被纤维结缔组织取代。

“目前，慢性乙型肝炎无法治愈。我们现在已经能够证明，开发新技术的T细胞疗法为治疗由病毒引发的慢性HBV感染和肝癌提供了一个令人鼓舞的解决方案。 Œ生活药物¹是我们目前最有效的治疗方法，“Ulrike Protzer教授解释道。她是慕尼黑亥姆霍兹中心和慕尼黑技术大学病毒学研究所所长，他们都是德国感染研究中心（DZIF）的成员。
T细胞消除乙型肝炎

该研究的第一作者和Ulrike Protzer小组的科学家Karin Wisskirchen博士表示，新的T细胞疗法是专门针对抗HBV感染和HBV相关肝癌的方法而开发的。已知在慢性感染的患者中，病毒特异性T细胞不能被检测到或者它们表现出活性降低。然而，如果患者能够自己控制病毒，则可以检测到强烈的T细胞反应。 “明显的答案是使用病毒特异性T细胞来弥补这一缺陷，”Wisskirchen博士说。 HBV特异性T细胞受体的遗传信息来自已解决感染的患者。在实验室中，然后可以将其从慢性乙型肝炎患者的血液中引入T细胞中。这导致形成新的活性T细胞，其对抗病毒或病毒诱导的癌细胞。以这种方式产生的T细胞能够完全消除细胞培养物中HBV感染的细胞。

与汉堡Maura Dandri教授领导的小组合作，然后在人源化小鼠模型中测试免疫细胞。单剂量的受体修饰的T细胞足以控制肝脏中的病毒。因此，T细胞仅攻击受感染的肝细胞并保护健康组织。 Myrcludex B是由海德堡的Stephan Urban教授开发的一种实验性药物，然后一旦T细胞停止循环就被用于防止病毒再次感染健康的肝细胞。结果，感染完全治愈。
临床研究的准备工作

“这项研究的有希望的结果将有助于我们进一步研究T细胞治疗的潜力，并与我们的合作伙伴一起进行临床试验。因此，我们正朝着建立这种形式的个性化医疗迈出决定性的一步，”Protzer教授说。因此，她的小组将继续探索将治疗方法应用于最广泛的患者群体的方法。 HelmholtzZentrumMünchen已将其部分T细胞疗法授权给SCG Cell therapy Pte。 “与我们的合作伙伴一起，我们正计划进行一项临床试验，以研究HBV相关性肝细胞癌患者的治疗，”Wisskirchen博士解释说。 T细胞疗法是一个高度创新的领域，由于临床试验在淋巴瘤治疗方面取得了巨大成功，因此获得了动力。丹德里教授强调：“如果没有我们在德国感染研究中心的密切合作，这种进步是不可能的