A Hybrid Platform Based on a Bispecific Peptide-Antibody Complex for Targeted Cancer Therapy
- 주제(키워드) antibodies , aptides , cancer therapy , fibronectin , peptide therapeutics
- 주제(기타) Chemistry, Multidisciplinary
- 설명문(일반) [Yu, Byeongjun; Jeon, Hyungsu; Kim, Hyungjun; Lee, Yonghyun; Keum, Hyeongseop; Kim, Jinjoo; Kim, Yujin; Jon, Sangyong] Korea Adv Inst Sci & Technol, Dept Biol Sci, Inst BioCentury, 291 Daehak Ro, Daejeon 34141, South Korea; [Lee, Yonghyun; Jon, Sangyong] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, 291 Daehak Ro, Daejeon 34141, South Korea; [Jon, Sangyong] Korea Adv Inst Sci & Technol, Ctr Precis Bionanomed, 291 Daehak Ro, Daejeon 34141, South Korea; [Hwang, Dobeen; Chung, Junho] Seoul Natl Univ, Coll Med, Dept Biochem & Mol Biol, 103 Daehak Ro, Seoul 03080, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 WILEY-V C H VERLAG GMBH
- 발행년도 2019
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000171977
- 본문언어 영어
- Published As https://dx.doi.org/10.1002/anie.201811509
초록/요약
Peptide-based therapeutics have suffered from a short plasma half-life. On the other hand, antibodies suffer from poor penetration into solid tumors owing to their large size. Herein, we present a new molecular form, namely a hybrid complex between a hapten-labeled bispecific peptide and an anti-hapten antibody (HyPEP-body), that may be able to overcome the aforementioned limitation. The bispecific peptide containing a cotinine tag was synthesized by linking a peptide specific to fibronectin extra domainB (EDB) and a peptide able to bind and inhibit vascular endothelial growth factor (VEGF), yielding cot-biPEP(EDB-VEGF). Simple mixing of cot-biPEP(EDB-VEGF) and anti-cotinine antibody (Ab(cot)) yielded the hybrid complex, HyPEP(EDB-VEGF). HyPEP(EDB-VEGF) retained the characteristics of the included peptides, and showed improved pharmacokinetic behavior. Moreover, HyPEP(EDB-VEGF) showed tumor growth inhibition with excellent tumor accumulation and penetration. These findings suggest that the hybrid platform described here offers a solution for most peptide therapeutics that suffer from a short circulation half-life in blood.
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