The bispecific antibody HB-32, blockade of both VEGF and DLL4 shows potent anti-angiogenic activity in vitro and anti-tumor activity in breast cancer xenograft models

Abstract

Increasing preclinical and clinical studies revealed that many tumor models had resistance to anti-VEGF-A and anti-VEGF-R2 therapies. Studies have shown that simultaneously blocked DLL4-Notch and VEGF signaling pathways can synergistically inhibit density and function of tumor blood vessels and reduce tumor growth rate. We successfully developed a bispecific monoclonal antibody (named HB-32) that targeting both human DLL4 and human VEGF. HB-32 showed high binding affinity to VEGF and DLL4. Furthermore, HB-32 inhibited proliferation, migration and tube formation of HUVEC. Finally, in vivo xenograft studies demonstrated that HB-32 inhibited proliferation of breast cancer cells (MDA-MB-231) and induced tumor cell apoptosis more efficiently than an anti-VEGF antibody or anti-DLL4 antibody alone. These findings indicate that our bispecific antibody provide a potential treatment for breast cancer.