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

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.