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- 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
- 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 domain B (EDB) and a peptide able to bind and inhibit vascular endothelial growth factor (VEGF), yielding cot‐biPEPEDB‐VEGF. Simple mixing of cot‐biPEPEDB‐VEGF and anti‐cotinine antibody (Abcot) yielded the hybrid complex, HyPEPEDB‐VEGF. HyPEPEDB‐VEGF retained the characteristics of the included peptides, and showed improved pharmacokinetic behavior. Moreover, HyPEPEDB‐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.
- Subjects
CANCER treatment; THERAPEUTIC use of immunoglobulins; VASCULAR endothelial growth factors; MOLECULAR biology; NANOMEDICINE
- Publication
Angewandte Chemie, 2019, Vol 131, Issue 7, p2027
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201811509