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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 吳漢忠 | zh_TW |
dc.contributor.advisor | Han-Chung Wu | en |
dc.contributor.author | 賴儀庭 | zh_TW |
dc.contributor.author | Yi-Ting Lai | en |
dc.date.accessioned | 2021-07-10T22:10:01Z | - |
dc.date.available | 2024-02-28 | - |
dc.date.copyright | 2018-10-09 | - |
dc.date.issued | 2018 | - |
dc.date.submitted | 2002-01-01 | - |
dc.identifier.citation | Park, S.Y., Bae, J.S., Cha, E.J., Chu, H.H., Sohn, J.S., & Moon, W.S. (2016). Nuclear EpICD expression and its role in hepatocellular carcinoma. Oncology Reports, 36, 197-204.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77583 | - |
dc.description.abstract | 單株抗體在過去這20幾年來一直是癌症診斷或治療上非常重要的發展方向。癌症抗體療法概念最初源自1960年代藉由血清學技術觀察到腫瘤細胞膜上各種抗原的存在,這些癌症抗原多半都具有過度表現或是突變的特性。上皮細胞黏附因子 (EpCAM)即是在抗體療法中良好的標的蛋白。目前發現許多上皮細胞癌都有EpCAM的高度表現,包括大腸直腸癌、乳癌、卵巢癌、胰臟癌與肺癌等。過去研究顯示EpCAM 的過度表達與腫瘤增生、轉移、侵襲,造成化療的抗性以及病患存活率降低有相當密切的關係。因此,發展專一性辨認上皮細胞黏附因子,並用於診斷或治療功能之單株抗體成為目前之趨勢。因此在本篇研究中,我們製備出十株單株抗體,其中八株EpAb21-1、EpAb23-1、 EpAb28-3、EpAb34-4、EpAb40-8、 EpAb41-9與EpAb42-1能夠專一性辨識細胞的上皮細胞貼附因子之膜外構造,另兩株EpAb19-24、 EpAb32-16與EpAb43-19能夠辨認上皮細胞貼附因子之膜內構造。除此,利用細胞早期凋亡試驗找出其中兩株EpAb23-1與EpAb34-4能夠誘發細胞凋亡,並利用流式細胞儀分析其凋亡機制,再以噬菌體呈現技術 (Phage display) 經由親和性篩選方法,從大量不同蛋白胜肽序列噬菌體中選取到專一結合EpAb34-4噬菌體株,用以了解抗體之抗原決定位。這些具高度專一與親和力之上皮細胞黏附因子之單株抗體,日後將可用於癌症之診斷或治療。 | zh_TW |
dc.description.abstract | In the past two decades, monoclonal antibody therapy for cancer has been a pivotal component in the diagnosis and treatment of cancer. The fundamental basis of antibody-based therapy for cancer was originally derived from the observation of the presence of various antigens on tumor cell membrane by serological techniques in the 1960s, and these cancer antigens are mostly characterized by overexpression or mutation. Epithelial cell adhesion molecule (EpCAM) is an emerging target in antibody-based therapy. EpCAM is overexpressed in a wide array of carcinomas such as breast cancers, ovarian cancers, pancreatic cancers and colon cancers. Numerous studies have shown that EpCAM overexpression enhances untoward malignant phenotypes of cancer cells, and reduce the survival of cancer patients. Therefore, it is rational and accretive to develop monoclonal antibodies against EpCAM for cancer theranostics. In this study, we generated ten monoclonal antibodies with high specificity to EpCAM via hybridoma. Among the 10 clones, seven of them bind to extracellular domain of EpCAM (EpEX), whereas the least of them target to the cytoplasmic tail of EpCAM (EpICD). Cell apoptosis assay was conducted and EpAb23-1 and EpAb34-4 were shown being capable to induce cancer cell apoptosis. Mechanisms of apoptosis was further elucidated through flow cytometry. Phage display technology was used to select the matching phage clones specific to EpAb34-4 from a large number of peptide library. In conclusion, we acquired apoptosis-inducing anti-EpCAM antibody with high affinity and specificity in this study, and it paves the way to further evolution into EpCAM-targeting cancer theranostics in the future. | en |
dc.description.provenance | Made available in DSpace on 2021-07-10T22:10:01Z (GMT). No. of bitstreams: 1 ntu-107-R05450014-1.pdf: 3773919 bytes, checksum: face1d86ba70cd1a0f2c783865b54460 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 口試委員會審定書 1
致謝…………………………………………………………………………...……….2 中文摘要…………………………………………………………………………...….3 Abstract 4 Contents 6 Contents of figures 9 Chapter 1 Introduction 10 1.1 Development of monoclonal antibody 10 1.1.1 Antibody therapy: direct and indirect effects 11 1.2 Epithelial cell adhesion molecule (EpCAM) 12 1.2.1 Structure of EpCAM 13 1.2.2 The oncogenic signaling of EpCAM 14 1.2.3 Expression pattern of EpCAM 15 1.2.4 The prognostic role of EpCAM in cancer 16 1.3 The therapeutic role of EpCAM in cancer 18 1.3.1 EpCAM targeted monoclonal antibodies 19 1.3.2 EpCAM-specific immunotoxins and CAR-T cells recognizing EpCAM 21 Chapter 2 Materials and Methods 23 2.1 Cell line and cell culture 23 2.2 Production of recombinant proteins 23 2.3 Immunoprecipitation of EpCAM 24 2.4 Generation of monoclonal antibody recognizing EpCAM 25 2.5 Screening of mAbs against EpCAM by Enzyme-linked immunosorbent assay 26 2.6 Identification of mAbs against EpCAM by flow cytometric analysis 26 2.7 Western blot analysis 27 2.8 Determination of monoclonal antibody class and subclass 28 2.9 Cell apoptosis assay 29 2.10 Analysis of the expression level of caspases in apoptotic cells 29 2.11 Identification of B-cell epitopes of mAbs by phage display 30 Chapter 3 Results 32 3.1 Generation of monoclonal antibodies against EpCAM 32 3.2 Characterization of anti-EpCAM mAbs 33 3.3 Determination of the isotype and subclass 34 3.4 Production of purified antibodies of selected hybridoma clones 34 3.5 Evaluation of binding affinities of purified mAbs 35 3.6 Evaluation of apoptotic effects of mAbs 36 3.7 Investigation of the apoptosis mechanisms induced by EpAb23-1 and EpAb34-4 37 3.8 Identification of B cell epitope of EpAb23-1 and EpAb34-4 38 Chapter 4 Discussion and Conclusions 40 Figures . 44 | - |
dc.language.iso | zh_TW | - |
dc.title | 研發對抗EpCAM單株抗體運用於癌症之診斷與治療 | zh_TW |
dc.title | Development of Anti-EpCAM Monoclonal Antibodies for Cancer Theranostics | en |
dc.type | Thesis | - |
dc.date.schoolyear | 106-2 | - |
dc.description.degree | 碩士 | - |
dc.contributor.coadvisor | 江俊斌 | zh_TW |
dc.contributor.coadvisor | Chun-Ping Chiang | en |
dc.contributor.oralexamcommittee | 林國儀;王逸平 | zh_TW |
dc.contributor.oralexamcommittee | Kuo-I Lin;Yi-Ping Wang | en |
dc.subject.keyword | 上皮細胞黏附因子,單株抗體,噬菌體呈現技術,癌症診斷治療, | zh_TW |
dc.subject.keyword | epithelial cell adhesion molecule,monoclonal antibody,phage display,cancer theranostics, | en |
dc.relation.page | 69 | - |
dc.identifier.doi | 10.6342/NTU201802329 | - |
dc.rights.note | 未授權 | - |
dc.date.accepted | 2018-08-02 | - |
dc.contributor.author-college | 醫學院 | - |
dc.contributor.author-dept | 口腔生物科學研究所 | - |
顯示於系所單位: | 口腔生物科學研究所 |
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