封面專題•COVER STORY 澳大新語•2020 UMAGAZINE 22 37 陳新教授是中醫藥和免疫學專家，其家族九代從事中醫，研究遍及免疫藥理學、免疫生物學和轉化醫學。加入澳大前 於美國國家腫瘤研究所任職十多年。 Prof Chen Xin is an immunologist and Chinese medical doctor whose family has practised Chinese medicine for nine generations. His research focuses on immunopharmacology, immunobiology, and translational medicine. Before joining UM, he worked for over a decade at the National Cancer Institute in the United States. 疫細胞會與腫瘤狼狽為奸，阻止其它免 疫細胞攻擊癌細胞，調節性T淋巴細胞 （Treg細胞）正是這些「叛徒」之一。 陳教授發現腫瘤壞死因子及其二型受體 （TNFR2）結合時會令Treg細胞激活 和增殖，間接促進腫瘤生長。他還提 出，如果阻斷TNFR2的信號傳遞，就能 大大降低Treg細胞的數量和功能，從而 有助提高免疫系統對抗癌症的能力。陳 教授這一原創性發現近年已獲世界各地 研究人員的驗證和支持。 歐美一些研究者和製藥公司已經在研製 多種抗體藥物，期待通過靶向TNFR2 而達到治療腫瘤的目的。陳教授團隊另 闢蹊徑，研究中藥和其它天然產物中 所含有的TNFR2抑制劑，希望以更便 宜、副作用更少的天然小分子化合物取 代TNFR2抗體藥物的作用。陳教授團 隊也篩選了一批中藥複方，從中發現一 種名為野黃芩苷的化合物在體外均有抑 制TNFR2的活性，並在小鼠腫瘤模型 中，觀察到該化合物通過提高抗腫瘤 免疫反應而抑制腫瘤生長。有關野黃 芩苷在這方面的應用已經申請了中國 和美國專利。 2020年初，陳教授開始與中國科學院 昆明植物研究所的研究人員合作，繼續 有關研究。陳教授說：「我們將合作研 究結構多樣性天然化合物庫，期望發現 更有效的TNFR2調節劑，從而提高癌症 免疫治療的效果。」 immunotherapy is not as simple as it sounds because some immune cells come to the aid of tumours rather than fight them. Among such ‘traitors’ are Regulatory T lymphocytes (Treg cells), which suppress other immune cells from attacking cancer cells. Prof Chen was the first to report that the interaction between the tumour necrosis factor (TNF) and its type-2 receptor (TNFR2) could activate and expand Treg cells to support the growth of tumours. According to Prof Chen, the blockade of the signalling of TNFR2 has emerged as a new strategy to eliminate Treg cells and consequently enhance immune responses against cancer. In recent years, researchers around the world have substantiated his pioneering findings. Researchers and pharmaceutical companies in Europe and the United States have tried to develop a variety of TNFR2 antibodies to treat tumours by targeting TNFR2. But Prof Chen’s team is taking a different approach, hoping to replace TNFR2 antibodies with natural small-molecule compounds that are more affordable and have fewer bothersome side effects. They are studying TNFR2 inhibitors from traditional Chinese medicinal herbs and other natural products. After screening a large number of Chinese herbs, his team has identified a promising compound known as ‘scutellarin’. This compound possesses in vitro and in vivo activity in inhibition of TNFR2 biological function and boosts the anti-tumour immune responses to suppress tumour growth, as shown in mouse tumour model studies. Following this discovery, Prof Chen and his fellow researchers have filed patent applications in China and the US for the related uses of scutellarin. To advance this study, Prof Chen started collaborating with researchers at the Kunming Institute of Botany, under the Chinese Academy of Sciences, in early 2020. ‘Together, we will study a library of structurally diversified natural compounds, in an attempt to identify more effective TNFR2 regulators for better cancer immunotherapy,’ he says.
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