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A Hybrid Platform Based on a Bispecific Peptide–Antibody Complex for Targeted Cancer Therapy
Author(s) -
Yu Byeongjun,
Hwang Dobeen,
Jeon Hyungsu,
Kim Hyungjun,
Lee Yonghyun,
Keum Hyeongseop,
Kim Jinjoo,
Lee Dong Yun,
Kim Yujin,
Chung Junho,
Jon Sangyong
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201811509
Subject(s) - bispecific antibody , cancer , cancer therapy , antibody , targeted therapy , peptide , medicine , cancer research , immunology , chemistry , monoclonal antibody , biochemistry
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‐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.