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研究生: 廖偲伃
Ssu-Yu Liao
論文名稱: 從專利主路徑分析觀察CAR-T技術在細胞基因治療的發展趨勢
The Development Trend of CAR-T Technology in Cell & Gene Therapies through Patent Main Path Analysis
指導教授: 管中徽
Chung-Huei Kuan
口試委員: 蘇威年
Wei-Nien Su
王俊傑
Chun-Chieh Wang
學位類別: 碩士
Master
系所名稱: 應用科技學院 - 專利研究所
Graduate Institute of Patent
論文出版年: 2021
畢業學年度: 109
語文別: 中文
論文頁數: 75
中文關鍵詞: 引用關係網絡主路徑分析輔助路徑嵌合抗原受體T細胞細胞免疫治療
外文關鍵詞: Network citation, Main path analysis, Auxiliary main paths, CAR-T, cellular immunotherapy
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  • 癌症治療中細胞與基因療法是未來重要的方法之一。根據America’s Biopharmaceutical Companies在最新一期的2020年Cell and Gene Therapies報告指出,截至2020年2月13日以前共有362項細胞/基因療法(cell and gene therapies)開發計畫正在進行中,相較於2018年的統計數目成長了約25% 。其中利用免疫反應進行的細胞與基因療法,更是因為CD19 CART成功應用在血液腫瘤治療上,使得使用基因修飾CAR-T對抗實體腫瘤之研究也越發盛行 。
    新興的醫療技術,適合從專利層面進行分析與觀察。因取得專利需要提供明確技術特徵,而專利文獻是取得這些技術資料最容易也最直接的來源。本研究因此利用專利分析探討CAR-T細胞免疫療法如何突破困境有效對抗實體腫瘤之演進。針對一個特定領域或科學來說,引用網絡能夠呈現出其發展歷史與演化過程,故使用主路徑分析方法(Main-Path Analysis)進行引用網路關係分析。
    主路徑分析開始CAR-T技術始終圍繞在解決細胞免疫治療中臨床的問題,無論是結構變化提升CAR的功能與效能、免疫應答細胞如何辨識、運送及存活下來,又或是周邊基礎技術的提升,都與臨床過程中所欲解決的問題息息相關。此外,輔助路徑雖然是以雙特異性抗體角度出發,但在議題的對照上,主路徑與輔助路徑的關係更像是CAR-T技術外免疫治療同步發展的衍伸應用。
    然而,細胞來源是CAR-T技術中根本的難題,從患者自體細胞分離出來的T細胞,到同種異體捐贈者分離出來的T細胞,期望具有能規模化大量製造以降低成本,並產出品質相對穩定且良好的細胞製劑。與此同時,透過針對不同腫瘤或是疾病的研究,整合性的治療設計,以期能加快CAR-T細胞免疫治療在臨床上的發展。
    治療癌症是一個複雜的多因素問題,必須同時解決多個問題,故要如何結合醫學和基礎科學各領域,經過一系列CARs的設計、免疫反應機制的籌畫,以及針對療程各階段的協調,整合性的治療方法才能兌現精準醫學中免疫細胞療法的願景。


    Cell and gene therapy in cancer treatment is one of the important methods in the future. According to America's Biopharmaceutical Companies' 2020 Cell and Gene Therapies report in the latest issue, as of February 13, 2020, a total of 362 cell/gene therapy development projects are in progress, which is an increase about 25% compared to the 2018. Among them, cell and gene therapy using immune response is also because of the successful application of CD19 CART in the treatment of hematological tumors, making the use of genetically modified CAR-T to fight solid tumors more and more popular.
    Emerging medical technology is suitable for analysis and observation from the patent level. Obtaining patents needs to provide clear technical features, and patent documents are the easiest and most direct source to obtain these technical information. This study therefore uses patent analysis to explore how CAR-T cell immunotherapy can break through the dilemma and effectively combat the evolution of solid tumors. For a specific field or science, the citation network can show its development history and evolution process, so this study uses the Main-Path Analysis method to analyze the relationship of the patent citation network.
    The main path analysis of CAR-T technology has always focused on solving clinical problems in cellular immunotherapy, whether it is structural changes that improve the function and effectiveness of CAR, how immune response cells are identified, transported and survived, or the improvement of peripheral skills. All are closely related to the problems to be solved in the clinical process. In addition, although the auxiliary main pathway is dominated by bispecific antibodies, the development issue between the primary pathway and the auxiliary pathway is more like an extended application of immunotherapy outside the CAR-T technology.
    However, the source of cells is the fundamental problem of CAR-T technology. By separating T cells from autologous patients to allogeneic donors, it is hoped that not only the cost of large-scale production can be reduced, but also stable production can be achieved. At the same time, through the study of different tumors or diseases, the use of design and integrated treatment methods to accelerate the clinical development of CAR-T cell immunotherapy.
    Only integrated treatment methods can achieve the vision of immunotherapy in precision medicine. Because the treatment of cancer is a complex multi-factor problem that must be solved at the same time, how to combine the various fields of medicine and basic sciences, and go through a series of CARs design and immune response mechanism planning to achieve coordination of various stages of treatment .

    目錄 圖表索引 第1章 緒論 第1.1節 研究背景 第1.2節 研究動機與目的 第1.3節 研究架構 第2章 文獻探討 第2.1節 CAR-T細胞免疫療法介紹 第2.1.1節 CAR-T細胞物之結構介紹 第2.1.2節 目前CAR-T細胞免疫療法遇上的困境 第2.2節 CAR-T專利分析文獻探討 第2.3節 主路徑分析介紹 第3章 分析方法 第3.1節 資料來源 第3.2節 資料蒐集與關鍵字檢索 第3.3節 專利引用網路建立與觀察 第3.4節 主路徑與其他路徑找尋 第4章 研究結果與分析 第4.1節 專利文獻分析 第4.2節 專利主路徑分析 第4.2.1節 CAR-T技術專利引用網絡路徑識別 第4.2.2節 CAR-T技術專利引用網絡路徑演進解析 第4.2.3節 主路徑和其他主路徑間探討 第5章 結論與建議 第5.1節 CAR-T技術發展結論與預測 第5.2節 研究限制與未來建議 參考文獻 附錄

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