科技部新聞稿

全球首創導彈式癌症專一性標靶胜肽技術平台

精準殲滅癌細胞

日期：109年4月22日

發稿單位：生命科學研究發展司

聯絡人：李慧欣博士

電話：(02)2737-7461

E-mail：hhlee@nstc.gov.tw

目前使用的許多抗癌藥物，常常因為缺乏對癌細胞的專一性，造成正常組織受損，導致患者身上難以忍受的副作用。如能將抗癌藥物裝備了具有癌症專一性的標靶胜肽，將如同”導彈”一般，具備針對癌症之導向功能(附圖)，可提升該藥物在體內的傳遞與藥物進入癌細胞之效率，成為更有效的癌症標靶治療。

在科技部「再生醫學科技發展計畫」(106-109年度)及「新型態產學研鏈結計畫-價創計畫」(106-108年度)對跨國、跨領域整合性研究的支持下，林口長庚醫院游正博特聘講座教授利用創新的電腦模擬輔助方法，包括他們研發的HotLig(註一)，預測胜肽分子與其特殊癌症細胞表面的接受體之結合模型，經過優化處理癌症標靶胜肽之組成，提升該胜肽與癌症細胞接受體的互動與結合，研發出全球首創新世代癌症專一性標靶胜肽技術平台(FnCTP平台)；這些新穎的標靶胜肽經由分子接合方式嵌入癌症診斷治療的製備工作，建立適用於多種癌症兼可殲滅癌症幹細胞的新抗癌療法(註二；註三)。

游正博教授團隊證實FnCTP癌症標靶胜肽至少可廣泛地辦識至少11種癌症，包括：卵巢癌、胃癌、肺癌、肝癌、乳癌、大腸癌、胰臟癌等等，甚至是癌症幹細胞，但卻不會與正常細胞結合，其廣效性及安全性遠遠大於一般抗體藥物。同時，與現今癌症治療法，例如化學療法等，有顯著不同之處。這些廣泛性癌症標靶胜肽FnCTP技術平台可應用於多種癌症的治療，其專一性可以減少副作用。同時，以最佳化的癌症標靶胜肽FnCTPs為”導彈”，可利用導彈原理接上不同”彈藥”，如雙特異性抗體、單株抗體、小分子、放射性同位素、反義寡核苷酸、CAR-T等各種不同應用方式之創新抗癌藥物(附圖)，可適用於多種癌症兼可殲滅癌症幹細胞，可以滿足現今醫療迫切之需求，為全球首創的癌症療法，具有許多突破性優勢。此外，在科技部計畫支援下，利用該技術平台結合生物技術開發中心的雙特異性抗體專利，已研發出創新的FnCTP-BsAb雙特異性抗體。在癌症細胞株及動物試驗下證實，FnCTP-BsAb不但可近距離活化T細胞而直接毒殺癌細胞，免疫活化的區域也僅侷限於癌組織周圍，避免全身性免疫活化所造成類似自體免疫之副作用。該技術平台於2019獲得第16屆學研新創組國家新創獎。未來一旦該FnCTP-BsAb概念驗證(proof-of-concept)在臨床上獲得證實，癌症標靶胜肽FnCTP技術平台之未來應用性將充滿潛力。

另外，從經濟産業效益方面來看，經由科技部價創計畫以及長庚醫院與大學共同輔導下，游正博教授與陳鈴津院士共同於2019年成立新創公司-友生泰生醫股份有限公司(UCT Bioscience)，並成功地延攬前生技中心生藥所所長吳佳城博士為執行長。同時，也在同年12月完成長庚與友生泰生醫之技轉案，由友生泰生醫取得FnCTP技術平台之專屬授權。目前正在研發適用於臨床多種癌症的創新癌症免疫療法。新公司將先集中全力於一至兩種癌症，再拓展到數個癌症市場的高占有率，有別於傳統性的單一癌症治療的低市場占有率。

    游正博教授為國際上幹細胞與再生醫學領域之傑出研究學者，其研究著重於幹細胞與癌症領域的探討，並將成果轉譯至再生醫學與癌症治療上。目前除了與國衛院生藥所建立共同研發的機制，擴展該技術平台；2019年7月16日臺灣科技部-美國國家衛生研究院(NIH)雙邊科技合作會議，游正博教授更以科技部「再生醫學科技發展計畫」代表身份，在陳良基部長的見證下與美國NIH下的國家癌症研究所(NCI) Director Dr. Douglas R. Lowy達成雙邊合作案，同年11月間己經選派我方博後人員前往美國NCI Dr. Ira Pastan實驗室，利用此FnCTP専利平台，結合NCI所持有的抗癌毒素技術，進行另一波創新癌症毒素療法的研發。

 科技部近年來積極推動再生醫學科技發展跨領域整合性的研究，促進臺灣生醫資源和科技優勢的跨校資源整合，期望未來透過此跨國雙邊合作，加速癌症療法研發，幫助更多病友。

參考文獻：

註一: HotLig: a molecular surface-directed approach to scoring protein-ligand interactions. https://pubs.acs.org/doi/abs/10.1021/ci400302d

註二: Structure-based optimization of GRP78-binding peptides that enhances efficacy in cancer imaging and therapy. https://www.sciencedirect.com/science/article/pii/S0142961216300904?via%3Dihub

註三: Structure-based design for binding peptides in anti-cancer therapy. https://www.sciencedirect.com/science/article/pii/S0142961217307561?via%3Dihub
 

研究成果聯絡人

游正博 特聘講座教授 John Yu, M.D., Ph.D.

林口長庚紀念醫院幹細胞與轉譯癌症研究所所長

林口長庚紀念醫院細胞治療中心主任

長庚大學特聘講座教授

中央研究院細胞與個體生物學研究所客座講座

聯絡電話(公)：03-3281200 #7803

電子郵件信箱：johnyu@cgmh.org.tw

Press Release

April 22, 2020

Novel Anti-Cancer Therapeutics Using Universal Cancer Targeting Peptide Platform Technologies

        The global market of cancer drugs in 2017 was valued at $104 billion (Evaluate, May 2018). Annual global growth in the market is expected to be 12.2 % through 2024, reaching a total of $233 billion. Recent progress in the identification of new cancer targets has widened the scope of anti-cancer therapeutics from conventional chemotherapy or radiotherapy to molecularly targeted drugs. However, without a “guiding missile” for cancer targeted delivery, many of such anticancer therapeutics lead to damage of normal tissues that patients find hard to tolerate. Ideally, anticancer therapeutics carrying payloads of drugs equipped with cancer-targeting peptides (CTPs) as “guided missiles” should enable targeted delivery to cancer cells.

        With the support of Ministry of Science and Technology in Taiwan (MOST), Dr. John Yu, Distinguished Chair Professor and Director, Institute of Stem Cell and Translational Cancer Research at Chang Gung Memorial Hospital in Linkou, used computer-aided methods and novel scoring algorithms, such as HotLig, for the rational design of cancer-targeting peptides. John Yu’s group has shown that these CTPs can guide various types of therapeutics to target many types of cancers. In addition to small molecules and radioactive isotopes, therapeutics such as DNA, RNA and liposomal drugs can all be conjugated with these peptides. CTPs can also be used to replace antibodies to generate immunotherapeutics such as bispecific antibodies and immunotoxins. Existing “targeted’ therapeutics for cancer patients usually focused on a few selected cancers. John’s patented “Fn Cancer Targeting Peptide” (FnCTP) technology not only has cancer specificity, it is currently the only technology that can be widely applied in a variety of cancers and can also target cancer stem cells. These features provide great advantage over existing therapeutics in fulfilling the unmet medical needs.

    Through a series of computer simulation and amino acid sequence optimization of the selected first generation CTPs, the researchers successfully developed a new generation of FnCTP technology that has high cancer specificity. The research team has demonstrated that FnCTPs can identify at least 11 cancer types, including ovarian, gastric, lung, liver, breast, colorectal, pancreatic cancers etc., but will not bind to healthy breast, peripheral blood, vascular endothelial cells, and dermal fibroblasts. In 2019, the research team for this universal FnCTP platform technologies received the 16th National Innovation Award. In the same year, a new UCT Bioscience Co. was set up to develop novel anticancer drugs using this FnCTP core technology platform. Dr. Chia-Cheng Wu from Development Center of Biotechnology was recruited as the CEO of this new biomedical company. Last Dec, UCT Bioscience Co. received the exclusive technology transfer of FnCTP platform from Chang Gung Memorial Hospital. The company hopes to provide cancer patients targeted drugs that are effective with little side effects, to improve their chances of survival with better quality of life.

        Dr. Yu is an internationally renowned researcher in stem cell biology and regenerative medicine. His research focuses on the identification of unique markers/regulators from stem cells and cancer stem cells, in order to develop new theranostics for cancer and anticancer therapy. On July 16 2019, he was invited to attend the MOST-NIH bilateral Science/Technology conference at NIH, Washington DC. Subsequently, he successfully worked out a collaborative project with National Cancer Institute, NIH. Specifically, he is currently working on a new anticancer therapeutics using the proprietary FnCTP platform and the NIH’s technology of Moxetumomab Pasudotox. Last November, one of his postdoctoral fellows worked in Dr. Ira Pastan’s lab at NIH to explore this possibility of developing new immunotoxin. He anticipated that this therapeutic FnCTP-PE38 fusion protein would target a broad spectrum of cancer types, including cancer stem cells.

        In recent years, MOST has fostered multidisciplinary collaboration to promote the progress of regenerative medicine research. Such integration of biomedical resources, cross-disciplinary cooperation and international collaboration should facilitate a rapid development of anticancer therapeutics for the unmet medical need in Taiwan.

Author Information:

John Yu, M.D., Ph.D.

        John Yu is the Distinguished Chair Professor/Director, Institute of Stem Cell/Translational Cancer Research, and Cell Therapy Center, Chang Gung Memorial Hospital, Taiwan. He is also Distinguished Visiting Research Fellow at Institute of Cellular & Organismic Biology, Academia Sinica, and was the Director for the same Institute (2002-2009). He is the founding President for Taiwan Society for Stem Cell Research. Dr. Yu was elected to serve in many ISSCR Committees USA, the Steering Committee of Asia-Pacific Stem Cell Network, and advisor for Stem Cell Biology, Kumamoto Univ. He was Director of Exp. Hematology (1998-2002) at Scripps Research Institute, USA. He received an Established Investigatorship Award from American Heart Assoc. and many other awards.

Media Contact

Dr. John Yu

Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Linkou, Taiwan

TEL: 03-328-1200 ext.7803

Email: johnyu@gate.sinica.edu.tw

Dr. Hui-Hsin Lee

Department of Life Sciences, Ministry of Science and Technology

TEL: 02-27377461

Email: hhlee@nstc.gov.tw