HKBU-led Research Team Develops Novel Anti-viral Targeted Drug for Nasopharyngeal Cancer Treatment

香港浸会大学领导的研究小组开发新的抗病毒药物治疗鼻咽癌

2020-05-12 02:30:22 CISION

本文共1325个字,阅读需4分钟

A research team led by Hong Kong Baptist University has developed a novel anti-Epstein-Barr virus drug that can selectively disrupt a viral protein produced by EBV, leading to the shrinkage of tumours caused by the virus. It is the first known agent to successfully target the virus and disturb its latency in tumour cells in this way. The strategy of reactivation of EBV from its latency is a new trend in nasopharyngeal carcinoma (NPC) therapy, and some non-specific, anti-viral drugs have recently entered phase one or phase two clinical trials. Our new drug represents the first specific targeted agent to disrupt a single viral protein and to potently reactivate EBV from its latency. These research results were published in the international journal Proceedings of the National Academy of Sciences. EBV infection can lead to cancer EBV is a human herpesvirus that spreads through close person to person contact. It has infected more than 90% of the human population worldwide. The human immune system usually suppresses the EBV activity effectively, but in some people the virus continues to exist in the human body and becomes a risk factor for many cancers, such as post-transplant lymphoproliferative disease, Hodgkin lymphoma, Burkitt lymphoma, T/Natural Killer cell lymphomas, some gastric carcinoma, and NPC — a highly prevalent cancer in Hong Kong and southern China. In search of new therapies for EBV-related carcinomas, a research team comprising Professor Gary Wong Ka-Leung, Head of the Department of Chemistry, HKBU; Professor Mak Nai Ki, Professor, Department of Biology, HKBU; Dr Lung Hong Lok, Assistant Professor, Department of Chemistry, HKBU; and Dr Jiang Lijun, Research Assistant Professor, Department of Applied Biology and Chemical Technology at The Hong Kong Polytechnic University, developed a novel drug which has shown promising results in an animal model. Novel drug binds and disrupts vital EBV protein EBNA1 is the viral protein which is expressed in all EBV-associated tumour cells. EBNA1 plays a vital role in the maintenance of the viral genome and the proliferation of EBV-infected tumour cells. The research team constructed a new peptide drug with higher affinity to the EBNA1 protein, leading to the disruption of the structure and functions of EBNA1. The tumour cells will thus stop proliferating and die eventually. Furthermore, the study also showed that the new drug emits unique responsive fluorescence signals once bound with EBNA1 or its metal cofactor. The imaging results demonstrated that the drug can enter the nucleus of EBV-infected cells, where EBNA1 resides, to inhibit their growth and division. It could also potentially be applied to tumour cell imaging in the human body. Reactivating EBV After EBV infection, the virus can establish latent infection, remain hidden in the infected cells, and promote pathogenic development of the tumour cells. Disruption of EBV latent and induction of EBV lytic cycle is one of the current strategy to control of EBV-associated malignancy. As a result, the EBV-infected cells will die and will be eliminated by the immune system. The research team discovered that the new drug can reactivate EBV lytic cycle through the disruption of EBNA1, and provides a new mentality of treatment of NPC.   Testing the new drug in a mouse model The research team tested the new drug in an animal model by injecting it into mice with heavy tumour burden of EBV-positive nasopharyngeal tumours. The new drug could restore the body weights of the mice in the treatment group to healthy levels and it completely shrank the tumours in 70 days. The survival rate was also remarkably raised to 86% for the treatment group while it was only 6% for the control group without any treatment. "This discovery lays a good foundation for the development of therapeutics for the treatment of EBV-associated diseases such as NPC," said Professor Gary Wong Ka-Leung. Way forward Patents have been filed for the new drug and its previous generation. Based on these patents, HKBU researchers have established a HKBU spin-off company, called BP InnoMed Limited, with startup support from the Technology Start-up Support Scheme for Universities, and the new company aims to further develop the drug and carry out clinical trials. Media enquiries: Wong Suk-ling, Communication and Public Relations Office (Tel: 3411-2119, Email: [email protected]) SOURCE Hong Kong Baptist University (HKBU)
香港浸会大学( Hong Kong Baptist University )领导的一个研究小组开发了一种新型抗爱泼斯坦-巴尔病毒药物,可选择性阻断 EB 病毒产生的病毒蛋白,导致病毒引起的肿瘤缩小。它是第一个已知的代理人成功地瞄准病毒和干扰其潜伏期在肿瘤细胞的这种方式。 EBV 潜伏期的再激活策略是鼻咽癌( NPC )治疗的新趋势,一些非特异性抗病毒药物最近进入一期或二期临床试验。我们的新药代表了第一个特定的靶向药物,以破坏单一的病毒蛋白,并有效地激活 EBV 的潜伏期。这些研究结果发表在国家科学院国际期刊上。 EBV 感染可导致癌症 EBV 是一种人类疱疹病毒,通过近人接触传播。它已经感染了全世界90%以上的人口。 人类免疫系统通常有效地抑制 EBV 活性,但在某些人中,病毒继续存在于人体内,并成为许多癌症的危险因素,如移植后淋巴增生性疾病、霍奇金淋巴瘤、伯基特淋巴瘤、 T /自然杀伤细胞淋巴瘤、某些胃癌、NPC ——一种在香港和中国南方非常流行的癌症。 香港浸会大学化学系系主任黄家梁教授、香港浸会大学生物系教授麦乃基教授、香港浸会大学化学系助理教授龙鸿乐博士、香港浸会大学化学系助理教授蒋利君博士、香港理工大学应用生物与化学技术系研制了一种新型药物,在动物模型中显示出了良好的效果。 新型药物结合和破坏重要的 EBV 蛋白 EBNA1是在所有 EBV 相关肿瘤细胞中表达的病毒蛋白。EBNA1在病毒基因组的维持和 EBV 感染肿瘤细胞的增殖中起着至关重要的作用。 研究小组构建了一种与 EBNA1蛋白具有较高亲和力的多肽新药,导致 EBNA1的结构和功能受到破坏。因此肿瘤细胞将停止增殖并最终死亡。 此外,研究还表明,一旦与 EBNA1或其金属辅因子结合,这种新药就会发出独特的反应荧光信号。成像结果表明,该药物可以进入 EBNA1所在的 EBV 感染细胞的细胞核,以抑制其生长和分裂。它还可能应用于人体肿瘤细胞成像。 激活 EBV EBV 感染后,病毒可以建立潜伏感染,留在感染细胞内,促进肿瘤细胞的致病性发展。阻断 EBV 潜伏和诱导 EBV 裂解循环是目前控制 EBV 相关恶性肿瘤的策略之一。因此, EBV 感染的细胞将死亡,并将被免疫系统消灭。研究小组发现,该新药可以通过破坏 EBNA1激活 EBV 裂解循环,并提供了治疗 NPC 的新思路。 用鼠标模型测试新药 研究小组在动物模型中对这种新药进行了测试,将其注射到患有 EBV 阳性鼻咽肿瘤的小鼠体内。该新药可使治疗组鼠的体重恢复到健康水平,并在70天内使肿瘤完全缩小。治疗组的生存率也显著提高到86%,对照组无任何治疗的生存率仅为6%。 黄家梁教授表示:「这项发现为开发治疗 EB 病毒相关疾病(如鼻咽癌)的药物奠定了良好的基础。」 前进的道路 该新药及其上一代的专利已经申请。基于这些专利,浸大研究人员在大学科技创业支援计划的启动支援下,成立了一家香港浸大拆分公司,名为 BP InnoMed Limited ,新公司旨在进一步开发该药物及进行临床试验。 传媒查询: 黄素玲通讯及公共关系处(电话:3411-2119,电邮:[电邮保护]) 香港浸会大学(浸会大学)

以上中文文本为机器翻译,存在不同程度偏差和错误;偶尔因源网页结构局限,内容无法一次完整呈现。请理解并参考原站原文阅读。

阅读原文