Abstract Antibodies have been used for cancer therapy for two decades, but they suffer from poor localization and penetration into solid tumors because of their large size. Peptides can be an alternative for treatment of solid tumors due to their small size. However, therapeutic use of peptides is limited because of their short plasma half-life. We present a new molecular platform based on a hybrid complex between bispecific peptide and antibody, designated as HyPEP-body, composed of bispecific peptides labeled with a hapten as a pharmacophore and an anti-hapten antibody. Two different peptides are joined together with linker and then, labeled with the hapten. The bispecific pharmacophore are bound to the anti-hapten antibody through antigen-antibody interaction. The pharmacophores which can be chemically optimized or replaced with other peptides are in charge of therapeutic function, while the antibody imparts long plasma half-life. As a model study, we constructed HyPEP-body that simultaneously binds extra domain B (EDB) and vascular endothelial growth factor (VEGF) with EDB binding peptide, VEGF binding peptide, cotinine and anti-cotinine antibody. Complexation with the antibody extended the plasma half-life of the bispecific pharmacophores. Furthermore, bispecific pharmacophores released from the antibodies distributed more widely in the tumor tissue than the antibodies. Finally, treatment of the HyPEP-body inhibited tumor growth in U87MG, human glioblastoma, xenograft mouse model. This versatile hybrid platform will enhance the value of peptide therapeutics and suggest an innovative solution to the development of bispecific antibodies that has suffered from productivity issues. Citation Format: Byeongjun Yu, Dobeen Hwang, Sangyong Jon, Junho Chung. Hybrid complex between bispecific peptide and antibody for targeted cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2999.