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방사선종양학
- 2018년 05월호
[J Control Release.] A dimeric form of a small-sized protein binder exhibits enhanced anti-tumor activity through prolonged blood circulationKAERI, KAIST / 김태윤, 서효덕, 이동은*, 김학성*
- 출처
- J Control Release.
- 등재일
- 2018 Apr 23
- 저널이슈번호
- 279:282-291. doi: 10.1016/j.jconrel.2018.04.039. [Epub ahead of print]
- 내용
Abstract
Small-sized non-antibody scaffolds have attracted considerable interest as alternatives to immunoglobulin antibodies. However, their short half-life is considered a drawback in the development of therapeutic agents. Here we demonstrate that a homo-dimeric form of a repebody enhances the anti-tumor activity than a monomeric form through prolonged blood circulation. Spytag and spycatcher were genetically fused to the C-terminus of a respective human IL-6-specific repebody, and the resulting two repebody constructs were mixed at an equimolar ratio to produce a homo-dimeric form through interaction between spytag and spycatcher. The homo-dimeric repebody was detected as a single band in the SDS-PAGE analysis with an expected molecular size (78 kDa), showing high stability and homogeneity. The dimeric repebody was shown to simultaneously accommodate two hIL-6 molecules, and its binding affinity for hIL-6 was estimated to be comparable to a monomeric repebody. The serum concentration of the dimeric repebody was observed to be about 5.5 times higher than a monomeric repebody, consequently leading to considerably higher tumor suppression effect in human tumor xenograft mice. The present approach can be effectively used for prolonging the blood half-life of small-sized protein binders, resulting in enhanced therapeutic efficacy.
Author informationKim TY1, Seo HD1, Lee JJ2, Kang JA3, Kim WS3, Kim HM3, Song HY3, Park JM3, Lee DE4, Kim HS5.
1
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
2
Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea.
3
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup, Jeonbuk 580-185, Republic of Korea.
4
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup, Jeonbuk 580-185, Republic of Korea. Electronic address: delee@kaeri.re.kr.
5
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. Electronic address: hskim76@kaist.ac.kr.
- 키워드
- Blood circulation time; Homo-dimer; Repebody; Spytag-spycatcher; Therapeutic efficacy
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