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엔도좀 탈출능이 향상된 종양 특이적 세포질 침투항체의 개발
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 김용성 | - |
| dc.contributor.author | 박재영 | - |
| dc.date.accessioned | 2022-11-29T02:31:58Z | - |
| dc.date.available | 2022-11-29T02:31:58Z | - |
| dc.date.issued | 2018-02 | - |
| dc.identifier.other | 26913 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/19443 | - |
| dc.description | 학위논문(석사)--아주대학교 일반대학원 :분자과학기술학과,2018. 2 | - |
| dc.description.tableofcontents | 1. Introduction 1 2. Material and methods 3 3. Results 9 3.1 Generation of EpCAM-specific Cytotransmab for targeting tumor tissue 9 3.2 Development of endosomal escape motif on VH-CDR3 of Cytotransmab 17 3.3 Generation of Cytotransmab with endosomal escape motif on both of VH-CDR3 and VL-CDR3 for improving endosomal escape efficiency 24 3.4 Improvement of biophysical properties of Cytotransmab with endosomal escape motif on both of VH-CDR3 and VL-CDR3 29 4. Discussion 39 5. References 43 국문 요약 46 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | 엔도좀 탈출능이 향상된 종양 특이적 세포질 침투항체의 개발 | - |
| dc.title.alternative | Generation of tumor-specific cytosol-penetrating antibody with improved endosomal escape activity | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.alternativeName | Jae-Yeong Park | - |
| dc.contributor.department | 일반대학원 분자과학기술학과 | - |
| dc.date.awarded | 2018. 2 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 800907 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000026913 | - |
| dc.subject.keyword | Cytosol-penetrating antibody | - |
| dc.subject.keyword | Endosomal escape | - |
| dc.description.alternativeAbstract | In general, Intact form of IgG antibodies cannot reach the cytosol by escaping from the endosome after receptor-mediated endocytosis because they have no endosomal escape activity. Our group recently reported the cytosol-penetrating antibody TMab4 cytotransmab. Also, we generated TMab4-3 which is an engineered version of TMab4 to improve the endosomal escape efficiency and its expression yield. However, TMab4-3 is not yet suitable for targeted therapy because TMab4-3 has a binding activity against HSPG expressed on the surface of normal cells. In addition, it is necessary to improve the endosomal escape efficiency to increase the therapeutic efficacy of cytotransmab. Here, I generated a tumor-specific cytotransmab with improved endosomal escape efficiency. First, I have created a new cytotransmab called as CT-41 with the elimination of HSPG binding activity. Second, a cyclic peptide for targeting EpCAM which is well known for over-expressed on surface of tumor cell was fused with N-terminus of CT-41 to confer tumor tissue specificity. Third, an additional endosomal escape motif for cytotransmab have been introduced into the EpCAM specific cytotransmab called as CT-ep41. Lastly, charged residue mutations are inserted near the hydrophobic endosomal escape motif to increase its developability and solubility. As a result, CT12-ep61 as a final clone is showed a specificity to EpCAM-positive tumor cells and increased endosome escape efficiency about 34% compared to CT-ep41 and its expression level is higher about 8-fold compared to CT-ep41. These results suggest that tumor-tissue specific cytotransmab can be applied as a tool for targeted cancer therapy. | - |
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- Graduate School of Ajou University > Department of Molecular Science and Technology > 3. Theses(Master)
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