浸大領導科研團隊研發新抗病毒標靶藥治療鼻咽癌
香港浸會大學（浸大）領導的科研團隊研發了一種嶄新的抗皰疹病毒第四型（EB病毒）藥物，能選擇性地破壞從人類EB病毒產生的蛋白，令由該病毒引起的腫瘤縮小。這是首次有藥物以這種方式干擾並對付潛伏在腫瘤細胞中的EB病毒。
重新激活潛伏在腫瘤中的EB病毒，是治療鼻咽癌的新趨勢，目前一些無靶向性的抗病毒藥物已進入第一或第二期臨床試驗。 浸大團隊發明的新藥是首次有標靶藥物可針對性破壞單一種病毒蛋白，從而有效地激活潛伏在鼻咽癌腫瘤的EB病毒。研究結果已在國際期刊《美國國家科學院院刊》發表。
EB病毒感染可引致癌症
EB病毒是一種人類皰疹病毒，通過人與人之間的接觸傳播，全球有九成多人口受EB病毒感染。人類的免疫系統通常能有效抑制EB病毒的活動，但在部份人身上會繼續存活，成為導致多種癌症的原因，例如移植後淋巴增生性疾病、霍奇金淋巴瘤、伯基特淋巴瘤、T/自然殺手細胞淋巴瘤、部分胃癌，以及在香港和華南地區非常普遍的鼻咽癌。
由浸大化學系系主任黃嘉良教授、生物系麥乃岐教授、化學系助理教授龍康樂博士、香港理工大學應用生物及化學科技學系研究助理教授江麗君博士組成的科研團隊，嘗試為EB病毒相關的癌症開拓新的治療方案，並研發出一種嶄新的藥物，在動物實驗的測試結果令人鼓舞。
新藥黏合並破壞EB病毒蛋白
EBNA1是病毒蛋白，表達在所有與EBV相關的腫瘤細胞中。EBNA1對維持EB病毒基因組，以及受EB病毒感染的腫瘤細胞大量增生起着重要作用。
研究團隊在設計這種以肽（peptide）為基礎的新藥結構時，增強了它黏合EBNA1蛋白的能力，從而破壞EBNA1的結構及功能，令潛伏的EB病毒以及腫瘤細胞停止生長，最終死亡。
此外，研究發現新藥與EBNA1或其金屬因子結合後，會發出獨特的熒光信號。熒光影像顯示，新藥能進入受EB病毒感染細胞的細胞核，即EBNA1的所在位置，並抑制其生長和分裂，這顯示新藥或能應用於人體腫瘤細胞成像。
新藥能激活EB病毒
感染EB病毒後，病毒會進入潛伏期及隱藏在被感染的細胞內，並促進腫瘤細胞的致病性發展。破壞EB病毒的潛伏能力並誘導它的裂解週期，是控制EB病毒相關惡性腫瘤的當前策略之一，目的是令感染EB病毒的細胞死亡，再被免疫系統清除。研究團隊發現，新藥能透過破壞EBNA1來重新激活潛伏的EB病毒，這發現為治療鼻咽癌提供了新概念。
動物實驗大幅提升存活率
研究團隊把新藥注射至老鼠體內以進行測試，這些老鼠均感染EB病毒而長出巨型的鼻咽癌腫瘤。結果顯示70天後，治療組老鼠的體重可回復至健康水平，腫瘤亦徹底收縮。而且，治療組老鼠的存活率大幅提升至86%，相對未經任何治療的對照組老鼠存活率僅有6%。
黃嘉良教授指出：「是項研究為發展與EB病毒相關的疾病，例如鼻咽癌的治療方案，奠定了良好的基礎。」
未來路向
研究團隊已為新藥及此前開發的相關新藥申請專利。在這些專利發明的基礎上，浸大研究人員成立了「BP InnoMed Limited」，並在大學科技初創企業資助計劃的支持下，為新藥作進一步研發，並進行臨床測試。
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HKBU-led research team develops novel anti-viral targeted drug for nasopharyngeal cancer treatment
A research team led by Hong Kong Baptist University (HKBU) has developed a novel anti-Epstein-Barr virus (EBV) 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.
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