UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES United States
Recent discoveries have demonstrated that the expression of LIGHT molecules within the tumor milieu counteracts cancer immune-evasion mechanisms and instigates activation and migration of T-cells into the tumor however the delivery of LIGHT to the tumor microenvironment has been a challenge. The overall goal of this project is to develop a targeted therapy that will deliver LIGHT to the tumor microenvironment by generating bispecific fusion proteins that are one-part LIGHT and one-part tumor-vasculature targeting antibodies specifically targeting Delta-Like Ligand 4 DLL4 and EphB4. In addition to LIGHT delivery, treatment with these antibodies alone has been shown to reduce tumor burden, which may enhance the effects of targeted LIGHT therapy. These bi-specific fusion proteins will be used, as proof-of-concept, to show that they lead to tumor eradication in both primary and advanced stage prostate cancer. In this annual report we summarize where we are in the production cycle and validation of these fusion proteins as well as provide a timeline for in vivo experiments.