Emerging reports suggest Delta-like-ligand 4 (DLL4) is a promising target to augment the effects of VEGF inhibitors. Simultaneous blockade of VEGF/VEGFR and DLL4/Notch signaling pathways leads to more potent inhibition of tumor progression by a synergic anti-angiogenic activity in various mouse xenograft models. We have developed a bispecific antibody targeting VEGF and DLL4 (ABL001, TR009) with similar in vitro biological and biochemical activities compared to each monoclonal antibody, e.g., binding affinities on each target, competitive inhibition abilities on ligand-receptor interactions, and inhibition effects on endothelial cell proliferation and DLL4-induced Notch1-dependent activation. In addition, ABL001 more efficiently inhibited the tumor progression of several cancer cell line derived xenograft models as well as patient-derived xenograft models than an anti-VEGF antibody or anti-DLL4 antibody alone. Currently the safety and tolerability of ABL001 are evaluating in clinical phase 1 trial (ClinicalTrials.gov Identifier: NCT03292783). In conclusion, ABL001 is being developed as a promising therapeutic bispecific antibody for cancer treatment.
Dr.Weon-Kyoo You received his PhD majored in Biochemistry at Yonsei University in 2004. Then, he worked as a postdoctoral fellow at UC San Francisco, and as a researcher at Sanford-Burnham Prebys Medical Discovery Institute from 2004 to 2012. He successfully performed several research projects and published many peer-reviewed papers in the field of tumor-induced angiogenesis and tumor microenvironments. After he came back to Korea, he joined at the Hanwha Chemical, R&D center as a principal research scientist to discover and develop a novel bispecific antibody until March, 2016. Currently he is working as the R&D Head at a startup biotech company, ABL Bio, Inc. and leading new antibody-based drug development projects.