Peptide-based therapeutics have suffered from a short plasma half-life. On the other hand, antibodies suffer from poor penetration in solid tumors owing to their large size. Here, we present a new molecular form-a hybrid complex between a hapten-labeled bispecific peptide and an anti-hapten antibody, designated HyPEP-body-that may be able to overcome the aforementioned limitation. A 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. The HyPEPEDB-VEGF retained the characteristics of the included peptides, and showed improved pharmacokinetic behavior. Moreover, The HyPEPEDB-VEGF showed tumor growth inhibition with excellent tumor accumulation and penetration. These findings suggest that the newly developed hybrid platform described here offers a solution for most peptide therapeutics that suffer from a short circulation half-life in blood.
Keywords: Anti-cotinine antibody, Aptides, Cancer therapy, Extra domain B of fibronectin, Peptide therapeutics