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A Hybrid Platform Based on a Bispecific Peptide-Antibody Complex for Targeted Cancer Therapy
- Title
- A Hybrid Platform Based on a Bispecific Peptide-Antibody Complex for Targeted Cancer Therapy
- Authors
- Yu, Byeongjun; Hwang, Dobeen; Jeon, Hyungsu; Kim, Hyungjun; Lee, Yonghyun; Keum, Hyeongseop; Kim, Jinjoo; Lee, Dong Yun; Kim, Yujin; Chung, Junho; Jon, Sangyong
- Ewha Authors
- 이용현
- SCOPUS Author ID
- 이용현
- Issue Date
- 2019
- Journal Title
- ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
- ISSN
- 1433-7851
1521-3773
- Citation
- ANGEWANDTE CHEMIE-INTERNATIONAL EDITION vol. 58, no. 7, pp. 2005 - 2010
- Keywords
- antibodies; aptides; cancer therapy; fibronectin; peptide therapeutics
- Publisher
- WILEY-V C H VERLAG GMBH
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- 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.
- DOI
- 10.1002/anie.201811509
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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