S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Biomedical Sciences (대학원 의과학과) Theses (Ph.D. / Sc.D._의과학과)
Development of a novel antibody-drug conjugate platform using a bispecific antibody
이중특이성 항체를 이용한 새로운 항체-약물 복합체 플랫폼의 개발
- 의과대학 의과학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의과학과, 2018. 8. 정준호.
- Antibody-drug conjugates (ADCs) are developed to selectively deliver cytotoxic agents to antigen-expressing
tumor cells as a new class of anticancer drugs and more potent than naked antibodies. However, optimization of the conjugation process between antibodies and cytotoxic agents and characterization of the ADCs are laborious and time-consuming processes. Here, we describe a novel ADC platform using a tetravalent bispecific antibody that simultaneously binds to the tumor associated antigen and a hapten conjugated to a cytotoxic agent. We selected cotinine as the hapten because it is not present in biological systems and is inert and nontoxic.
We prepared an anti-epidermal growth factor receptor (EGFR) × cotinine bispecific antibody and mixed it with an equimolar amount of cotinine-conjugated duocarmycin to form the ADC. This ADC showed significant in vitro and in vivo antitumor activity against EGFR-positive, cetuximab-refractory lung adenocarcinoma cells with KRAS mutations. These results suggest that tetravalent bispecific antibodies that simultaneously bind to tumor-associated antigens and cotinine could potentially be used drug carriers for selectively delivery of cotinineconjugated cytotoxic agents to the antigen-expressing tumor sites.
- Files in This Item: