화학공학소재연구정보센터
학회 한국공업화학회
학술대회 2022년 봄 (05/11 ~ 05/13, 제주국제컨벤션센터(ICC JEJU))
권호 26권 1호
발표분야 포스터-생물공학
제목 Antibody-Based Targeting of Cell Surface GRP94 Specifically Inhibits Cetuximab-Resistant Colorectal Cancer Growth
초록 Colorectal cancer (CRC) is one of the leading causes ofcancer death worldwide. Cetuximab, a human/mouse chimeric monoclonal antibody, is effective in a limited number of CRC patients because of resistance. Through phage display technology, we isolated a human antibody strongly binding to thecetuximab-resistant HCT116 surface and identified the target antigen as GRP94 usingproteomic analysis. Short interfering RNA-mediated GRP94 knockdown showed thatGRP94 plays a key role in HCT116 growth. In vitro studies revealed that the GRP94 antibody we developed strongly inhibits the growth of variouscetuximab-resistant CRC cell lines. We also demonstrated that GRP94 IgGmonotherapy significantly reduces HCT116 growth more potently compared tocetuximab, without severe toxicity. Therefore, cell surface GRP94 might be apotential novel therapeutic target in cetuximab-resistant CRC, andantibody-based targeting of GRP94 might be an effective strategy to suppress cetuximab-resistant CRC.



저자 김지웅, 조예빈, 양하림, 송진영, 유지은, 이석묵
소속 국민대
키워드 Cetuximab resistance; GRP94; Human antibody; Colorectal cancer
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