아주대학교

목차

I. INTRODUCTION 1
1. Structure and Physiological Function of Cadherin-17 (CDH17) 1
2. CDH17 Expression and Tumor-Associated Function in Gastrointestinal Cancers 1
3. Structural and Functional Segmentation of the CDH17 Extracellular Domain 6
4. Current Treatment Landscape and Drug Development Trends for Gastric Cancer 9
5. Molecular Rationale for Targeting CDH17 with ADCs 13
6. Current Progress and Limitations in CDH17-Targeted Antibody Therapeutics 14
7. Purpose and Significance of This Study 17
II. MATERIAL & METHOD 20
1. Analysis of CDH17 mRNA Expression and Overall Survival 20
2. Cell lines and cell culture 20
3. Generation of Anti-CDH17 Mouse Monoclonal Antibody 21
4. Enzyme-linked immunosorbent assay (ELISA) 22
5. Flow Cytometry 23
6. Internalization assay 24
7. Western blot analysis 24
8. Domain Mapping and Cross-Reactivity 25
9. Production of Chimeric Antibody 26
10. Surface plasmon response (SPR) assay 28
11. siRNA-mediated knockdown of CDH17 28
12. Wound-Healing Assay 29
13. Statistical analysis 29
III. RESULTS 31
1. Analysis of CDH17 Expression and Rationale for Antibody Development 31
2. Generation of mouse monoclonal antibodies against CDH17 36
3. Characterization of CDH17-Specific Monoclonal Antibody Candidates 42
4. Production and Purification of chimeric 4D6 antibody 49
5. Comparative Analysis of Chimeric 4D6 and Parental Antibody 53
6. Domain mapping and binding specificity of chi-4D6 antibody 61
7. Anti-migration effect of chi-4D6 antibody 66
IV. DISCUSSION 71
V. REFERENCES 75
VI. ABSTRACT IN KOREAN 79