화학공학소재연구정보센터
학회 한국공업화학회
학술대회 2019년 가을 (10/30 ~ 11/01, 제주국제컨벤션센터(ICC JEJU))
권호 23권 2호
발표분야 포스터_생물공학
제목 Development of an immunotoxin based on a full-length antibody via site-specific conjugation using a cysteine residue introduced to IgG and an unnatural amino acid
초록 Immunotoxins consisting of a toxin from bacteria or plants, and a targeting module have been developed as potent anti-cancer therapeutics. The majority of them, especially those in preclinical or clinical testing stages, are based on antibody fragments, even though the advantage of using full-length antibodies has been well documented. Here, we generated an immunotoxin via site-specific conjugation using a cysteine (Cys) residue introduced to IgG and a bio-orthogonally reactive unnatural amino acid. A Her2-targeting IgG, trastuzumab, was engineered to have an unpaired Cys at position 425 in the heavy chain, and an unnatural amino acid having the azido group (azidophenylalanine) was incorporated into an engineered Pseudomonas exotoxin A (PE24). The two protein molecules were conjugated site-specifically using a bifunctional linker having dibenzocyclooctyne and maleimide groups. The resulting trastuzumab-PE24 conjugate was cytotoxic to Her2-overexpressing cell lines.
저자 이병성1, 이유미1, 이상우1, 박지수1, 정보석1, 조미경2, 정상택3, 유태현1
소속 1아주대, 2국민대, 3고려대
키워드 immunotoxin; site-specific conjugation; immunoglobulin G; unnatural amino acid; Pseudomonas exotoxin A
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