(From left) Dr Gary Wong, Dr Lung Hong-lok, Miss Jiang Lijun and Professor Mak Nai-ki and their collaborators are the first in the world to develop a compound to enhance the detection of tumour cells and inhibit their growth in mice, providing insights for the development of therapeutics for use against EBV-associated diseases.


(左起)黃嘉良博士、龍康樂博士、江麗君小姐和麥乃岐教授與團隊全球首創一種化合物,優化現時用於偵測和抑制EB病毒腫瘤,研究有望應用於EB病毒的標靶治療。

The diagram shows the use of the designed probe for imaging and inhibition of EBV-infected tumours


團隊設計的「探針分子」進入腫瘤細胞後,對腫瘤產生抑制效果並可同時用作顯影劑

The study shows that the probe can lead to 93% growth inhibition of EBV-positive tumours in mice: (above) control tumour (below) tumour showing a 93% reduction in size.


探針分子有效抑制感染了EB病毒的老鼠腫瘤達93%,上圖是對照實驗,下圖是減少93%大小的三種不同老鼠腫瘤

Date: 13 Sep 2017 (Wednesday)

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HKBU scholars develop world-first dual imaging and inhibiting agent with high efficacy in suppressing EBV-associated tumours in mice

浸大學者研發全球首項具顯影及抑制EB病毒雙效探針     有望用於與EB病毒相關腫瘤的標靶治療

HKBU scholars along with their collaborators announced the world’s first chemical compound (probe) that can detect Epstein-Barr virus (EBV)-infected cells in mice, and simultaneously inhibit these tumour cells with an efficacy rate of above 90%. This discovery lays a good foundation for the development of therapeutics for use against diseases associated with EBV, including nasopharyngeal carcinoma which is prevalent in Southern China. The study was published in the renowned international journal Nature Biomedical Engineering.

The study showed that the probe containing the inhibitor luminesces when bound to the EBV encoded viral protein EBNA1 of EBV-infected cells in mice. It could thus be applied as an agent to detect the presence of tumours. The probe can also prevent the formation of EBNA1 homodimer and the study showed that the probe results in a 93% reduction in size of EBV-positive tumours in mice. With further development, this probe could potentially be used for imaging and suppression of human tumour cells.

The research team of this cross-disciplinary study is led by Associate Professor of HKBU Department of Chemistry Dr Gary Wong, and Professor of HKBU Department of Biology Professor Mak Nai-ki. Their collaborators, who are experts in various disciplines in HKBU, include Director of the Clinical Division of the School of Chinese Medicine Professor Bian Zhao-xiang, Research Assistant Professor of the Department of Biology Dr Lung Hong-lok, Senior Research Assistant of the Department of Chemistry Miss Jiang Lijun, as well as scholars of The Hong Kong Polytechnic University, The University of Hong Kong, and Durham University and University of Birmingham in the UK.

Dr Gary Wong said, “The establishment of EBV latency is closely associated with the oncogenic development of several human malignancies, including nasopharyngeal carcinoma. In the past few decades, EBNA1 has been considered an attractive target for anti-viral therapy, attracting a great deal of attention from researchers working in this community. Several studies on the inhibition of EBNA1, a dual-probe to track the EBNA1 at the nucleus level, were published but an agent with dual functions is still not yet available. Our team has developed the world’s first dual agent that can simultaneously perform imaging and suppress EBV-associated tumours.”

Dr Wong said he believes the study is not only a groundbreaking achievement, but also highly encouraging as the dual agent attains an efficacy rate of more than 90% in suppressing EBV-associated tumours. He added that with further development, this probe could potentially be applied to the imaging of tumour cells in the human body and lead to the development of therapeutics and enhance the overall efficacy of targeted therapeutics.

Dr Wong envisaged that scientists could make further developments on such probes since the zinc finger structure in EBNA1 homodimer is thought to contribute to the formation of EBNA1 homodimer.

This groundbreaking research project, entitled “EBNA1-targeted probe for the imaging and growth inhibition of tumours associated with the Epstein-Barr virus”, was published in the renowned international journal Nature Biomedical Engineering. (doi:10.1038/s41551-017-0042)

Nature Biomedical Engineering and Cell Chemical Biology published a commentary respectively highlighting the findings and significance of this study.

浸大與合作團隊全球首次研發出一種新的化合物,不單能偵測小鼠腫瘤細胞核內的「人類皰疹病毒第四型」(Epstein–Barr virus,EB病毒),更可同步抑制腫瘤生長逾九成。新化合物有望應用於EB病毒的標靶治療,包括華南地區發病感染率高的鼻咽癌。該項突破性研究已刊登於著名國際學術期刊《自然──生物醫學工程》。

研究結果發現,當團隊設計的化合物(包含抑制劑的「探針分子」)進入小鼠體內的腫瘤細胞,抑制劑與帶有病毒蛋白EBNA1結合後,可釋放出熒光訊號,因此可作為腫瘤的顯影劑,有助偵測腫瘤所在;而抑制劑在調控EBNA1同型二聚體形成的同時,亦能抑制EB病毒相關性腫瘤的生長達93%。因此,這探針分子有望能發展成既可檢測人體內的EB病毒腫瘤,又能同步抑制腫瘤的雙效能探針。

這項跨學科研究由浸大化學系副教授黃嘉良博士和生物系麥乃岐教授主導,成員來自浸大不同的專業範疇,包括中醫藥學院臨床部主任卞兆祥教授、生物系研究助理教授龍康樂博士、化學系高級研究助理江麗君小姐,以及來自香港理工大學、香港大學、英國杜倫大學和英國伯明罕大學的研究團隊。

黃嘉良博士說:「由於EB病毒的潛伏與多種人類惡性腫瘤,如鼻咽癌有密切關係,在過去數十年,很多研究人員探討以EBNA1作為抗病毒治療的標靶。現時,有不少偵測及追蹤癌症患者細胞核內EBNA1的探針,然而,今次是全球首次成功研發能同步偵測和抑制該腫瘤的雙重效能探針。」

黃博士相信,是次研究成果不單是偵測和抑制EB病毒腫瘤的一大突破,而合成物抑制腫瘤的有效率逾九成更令人鼓舞,他期望新合成物最終能應用於人體腫瘤偵測和治療上,令標靶治療更快速和更有效。

黃博士補充說,這類探針可再作改進,因為EBNA1同型二聚體中的鋅指結構被認為對於EBNA1二聚體的形成也有一定的作用。

該項突破性研究的論文「EBNA1-targeted probe for the imaging and growth inhibition of tumours associated with the Epstein-Barr virus」已刊登於著名國際期刊《自然──生物醫學工程》(doi:10.1038/s41551-017-0042)。

《自然─生物醫學工程》和《細胞化學生物學》亦分別發表了評論文章介紹是項研究的結果與科學意義。