Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 이은규 | - |
dc.contributor.author | 김원준 | - |
dc.date.accessioned | 2018-04-18T06:06:42Z | - |
dc.date.available | 2018-04-18T06:06:42Z | - |
dc.date.issued | 2018-02 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/68101 | - |
dc.identifier.uri | http://hanyang.dcollection.net/common/orgView/200000432313 | en_US |
dc.description.abstract | Antibody drug conjugate (ADC) is one of the topics for the next generation oncology therapeutics because of its higher therapeutic index and potency. ADC consists of three basic components: antibody, linker, and cytotoxic drug. Many research has tried to optimize the combination of these components through conventional solution-phase conjugation, which requires purified antibody for conjugating and also multi-steps of buffer exchange and purification after conjugation. Solid-phase conjugation, in which antibody is first immobilized to solid matrix by affinity interaction, reduced by a reducing agent to expose the reactive thiol groups, and then a drug-linker complex is specifically conjugated to the immobilized antibody through thiol-maleimide reaction followed by ADC elution from the matrix. Solid-phase conjugation could be a viable alternative since it would circumvent several post-conjugation purification steps, and eventually achieve a higher conjugation yield. Also, the immobilization step in solid-phase conjugation process could achieve purification and conjugation step simultaneously; i.e., it could synthesize ADC directly from antibody secreting cell culture broth. In this study, we used Herceptin® (antibody), SMCC (linker), and doxorubicin (drug) for ADC synthesis. We performed the solid-phase conjugation of ADC from purified antibody solution (“neat solution”) and culture broth mimicking solution. The results are identical indicating that the solid-phase conjugation process is not significantly interfered by the culture broth ingredients. We also confirmed the reproducibility of solid-phase conjugation process, and characterized the synthesized ADC by RP-HPLC, size exclusion chromatography (SEC), MALDI-TOF/TOF mass spectrometer, surface plasmon resonance (SPR), and cellular cytotoxicity test. Protein A-based solid-phase conjugation process shows ca. 20% higher yield than the conventional solution-phase conjugation process, which suggests solid-phase conjugation process is a feasible and attractive process for ADC synthesis directly from cell culture broth. | - |
dc.publisher | 한양대학교 | - |
dc.title | 고체상 접합기술을 이용한 항체-약물 복합체 (ADC)의 합성 | - |
dc.title.alternative | Application of solid-phase conjugation technology for synthesis of Antibody-Drug-Conjugate (ADC) | - |
dc.type | Theses | - |
dc.contributor.googleauthor | 김원준 | - |
dc.contributor.alternativeauthor | WONJUN KIM | - |
dc.sector.campus | S | - |
dc.sector.daehak | 대학원 | - |
dc.sector.department | 바이오나노학과 | - |
dc.description.degree | Master | - |
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