A Hybrid Platform Based on a Bispecific Peptide-Antibody Complex for Targeted Cancer Therapy

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.