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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49137
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dc.contributor.advisor翁啟惠(Chi-Huey Wong),吳宗益(Chung-Yi Wu)
dc.contributor.authorTzu-En Tsengen
dc.contributor.author曾子恩zh_TW
dc.date.accessioned2021-06-15T11:17:04Z-
dc.date.available2019-08-26
dc.date.copyright2016-08-26
dc.date.issued2016
dc.date.submitted2016-08-19
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49137-
dc.description.abstractGlobo-H has been found expressed on cancer cells and also cancer stem cells, but not expressed in normal cells. Recently, more than 16 different types of cancers have been found Globo-H positive, including 60-65% breast cancers. Therefore, Globo-H vaccine should have highly selective and efficient toward various cancers. Moreover, scientists have found that there are SSEA3 and SSEA4 expressed on the surface of cancer cells and also cancer stem cells, and both of SSEA3 and SSEA4 are not found in normal cells. Therefore, Globo-H, SSEA3 and SSEA4 are good antigens as cancer vaccines.
There are two generations of Globo-H cancer vaccine under clinical trial. First generation of Globo-H vaccine is Globo-H-KLH vaccine, under phase III clinical trial. Second generation of Globo-H vaccine are Globo-H-DT-QS21 and Globo-H-DT-C34, under phase I clinical trial and preclinical trial respectively. First generation of Globo-H vaccine induces mainly IgM antibodies, which makes it less favorable as a vaccine. However, Globo-H-DT-C34 has been found to have significantly IgG antibodies induced, so it should be a better cancer vaccine.
Further studies showed that over 98% of breast cancer patients express at least one of the three carbohydrate, Globo-H, SSEA4 and SSEA3, expressed on surface of cancer cells, so I wanted to make a divalent cancer vaccine of Globo-H and SSEA4.I used para-nitrophenol bifunctional linker to link Globo-H to DT. Afterwards, I used SBAP to attach SSEA4 to Globo-H-DT to afford Globo-H-DT-SSEA4.In another design, I tried to link Globo-H and SSEA4 to an amino acid respectively and then I will use solid phase peptide synthesis technique to control the proportion and distance of Globo-H and SSEA4. However, the following design isn’t finished yet, and I only finished the preparation of Globo-H building block. In sum, a divalent cancer vaccine of Globo-H and SSEA4 could be a new choice of carbohydrate-based cancer vaccines.
en
dc.description.provenanceMade available in DSpace on 2021-06-15T11:17:04Z (GMT). No. of bitstreams: 1
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Previous issue date: 2016
en
dc.description.tableofcontents謝誌 i
中文摘要 ii
Abstract iii
目錄 iv
表目錄 vi
圖目錄 vii
流程目錄 viii
簡稱用語對照表 ix
第一章 緒論 1
第一節 腫瘤相關醣類抗原 1
第二節 Globo-H的合成 4
第三節 Globo-H抗癌疫苗的發展 10
第四節 免疫佐劑的發展 14
第五節 本篇論文目標 16
第二章 結果與討論 17
第一節 Globo-H 的化學合成 17
2-1-1. 構築體6的合成 20
2-1-2. 構築體7的合成 21
2-1-3. 構築體8的合成 23
2-1-4. 構築體9的合成 24
2-1-5. 構築體3的合成 26
2-1-6. 雙醣構築體4的合成 27
2-1-7. 三醣構築體5的合成 28
2-1-8. Globo-H的一鍋化合成 29
第二節 SSEA4 的合成 31
2-2-1. 構築體46的合成 32
2-2-2. SSEA3 (化合物49)的合成 32
2-2-3. SSEA4 (化合物48)的酵素合成 34
第三節 Globo-H與SSEA4的二價癌症疫苗合成策略一 35
2-3-1. Globo-H monoester的合成 35
2-3-2. SSEA4-SH的合成 36
2-3-3. Globo-H與SSEA4的二價癌症疫苗合成策略一 37
第四節 Globo-H與SSEA4的二價癌症疫苗合成策略二 38
2-4-1. Globo-H天冬氨酸(aspartic acid)構築體62的合成 40
第五節 結論 42
第三章 實驗部分 43
第一節 一般方法 43
第二節 化學合成與結構鑑定 44
第四章 文獻參考 67
附錄:化合物之核磁共振光譜 75
dc.language.isozh-TW
dc.subject醣疫苗zh_TW
dc.subject癌症疫苗zh_TW
dc.subjectGlobo Hen
dc.subjectcarbohydrate-based anti-cancer vaccineen
dc.subjectcancer vaccineen
dc.subjectSSEA4en
dc.titleGlobo H與SSEA4的二價癌症疫苗製備zh_TW
dc.titlePreparation of a divalent cancer vaccine of Globo H and SSEA4en
dc.typeThesis
dc.date.schoolyear104-2
dc.description.degree碩士
dc.contributor.oralexamcommittee方俊民(Jim-Min Fang)
dc.subject.keyword癌症疫苗,醣疫苗,zh_TW
dc.subject.keywordGlobo H,SSEA4,cancer vaccine,carbohydrate-based anti-cancer vaccine,en
dc.relation.page95
dc.identifier.doi10.6342/NTU201603113
dc.rights.note有償授權
dc.date.accepted2016-08-20
dc.contributor.author-college理學院zh_TW
dc.contributor.author-dept化學研究所zh_TW
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