엔도좀 탈출능이 향상된 종양 특이적 세포질 침투항체의 개발

DC Field Value Language
dc.contributor.advisor김용성-
dc.contributor.author박재영-
dc.date.accessioned2022-11-29T02:31:58Z-
dc.date.available2022-11-29T02:31:58Z-
dc.date.issued2018-02-
dc.identifier.other26913-
dc.identifier.urihttps://dspace.ajou.ac.kr/handle/2018.oak/19443-
dc.description학위논문(석사)--아주대학교 일반대학원 :분자과학기술학과,2018. 2-
dc.description.tableofcontents1. 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.isoeng-
dc.publisherThe Graduate School, Ajou University-
dc.rights아주대학교 논문은 저작권에 의해 보호받습니다.-
dc.title엔도좀 탈출능이 향상된 종양 특이적 세포질 침투항체의 개발-
dc.title.alternativeGeneration of tumor-specific cytosol-penetrating antibody with improved endosomal escape activity-
dc.typeThesis-
dc.contributor.affiliation아주대학교 일반대학원-
dc.contributor.alternativeNameJae-Yeong Park-
dc.contributor.department일반대학원 분자과학기술학과-
dc.date.awarded2018. 2-
dc.description.degreeMaster-
dc.identifier.localId800907-
dc.identifier.urlhttp://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000026913-
dc.subject.keywordCytosol-penetrating antibody-
dc.subject.keywordEndosomal escape-
dc.description.alternativeAbstractIn 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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