아주대학교

목차

제1장 Introduction 1
제1절 Structure and function of interleukin-12 (IL-12) 1
제2절 IL-12 based Immunocytokines and the clinical trials 2
제3절 Binding site barrier 4
제2장 Materials and methods 5
제1절 Construction of expression plasmids 5
제2절 Expression and purification of Ab and immunocytokines 5
제3절 Size-Exclusion Chromatography (SEC) Analysis 6
제4절 Biolayer interferometry (BLI) 7
제5절 Cell culture 7
제6절 Flow cytometry 8
제7절 Preparation and activation of PBMC 8
제8절 IL-12 Receptor binding assay 9
제9절 PBMC Proliferation assay 9
제10절 Mice 10
제11절 Tumor inoculation and treatment 10
제12절 Biodistribution imaging in vivo and ex vivo 11
제13절 Immunohistochemistry (IHC) 11
제14절 Statistical analysis 13
제3장 Results 14
제1절 Design and engineering of anti-HER2 affinity-varying HCT-mono-mIL12 14
제2절 Measurement of HER2 binding kinetics of HCT-mono-mIL12 17
제3절 In vitro biochemical and biological activities of HCT-mono-mIL12 20
제4절 Evaluation of tumor targeting ability of HCT-mono-mIL12 22
제5절 HCT-mono-mIL12 inhibits HER2-positive tumors than HER2-negative tumors in vivo 26
제6절 In vivo antitumor effect of HCT-mono-mIL12 varies depending on affinity against tumor antigen 29
제7절 Tumor tissue distribution of HCT-mono-mIL12 depends on the anti-HER2 binding kinetics 31
제8절 HCT-mono-mIL12 expands the number of CD4+ and CD8+ TILs in tumor tissue 33
제9절 Mathematical analysis of behaviors of HCT-mono-mIL12 in solid tumor 36
제4장 Discussion 43
제5장 References 46