Delenex Therapeutics AG has announced new pre-clinical data demonstrating the efficacy of its DLX1008 antibody fragment in an in vivo model of Kaposi sarcoma.
DLX1008 is a monovalent anti-VEGF-A antibody fragment that binds with 20-30 picomolar affinity to both human as well as mouse VEGF-A. VEGF-A is a key mediator of neo-angiogenesis promoting tumor growth by enhancing the supply of the tumor mass with nutrients and oxygen.
Kaposi sarcoma is the most angiogenic cancer in the human population. It exists in a limited form where lesions develop predominantly on the skin only, and as a systemic disease, which is rapidly fatal, if untreated. Neutralizing VEGF-A starves the tumor by inhibiting neo-angiogenesis and by directly inhibiting tumor cell proliferation.
A team led by Prof. Dirk P. Dittmer from the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC had developed a xenograft mouse model based on Kaposi sarcoma associated herpesvirus-positive human endothelial cells. Such mice were intraperitoneally treated with DLX1008.
In these xenografted mice DLX1008 significantly retarded the tumor growth vis-à-vis a control group (p ≤ 0.004), and immunohistochemistry confirmed that the tumor died from the inside out in response to DLX1008.
Prof. Dittmer added that “this result is biologically even more impressive because of the biology of implant growth in this model. Cells on the outside of the skin implant will receive oxygen by passive diffusion as well as angiogenesis, the cells most dependent on angiogenesis are on the center of the implant.”
“DLX1008 is an excellent, highly potent antibody compound. As a result of its demonstrated antitumor activity, we will advance DLX1008 into clinical trials in oncological indications where angiogenesis plays a major role,” commented Thomas Hecht, MD, Executive Chairman of Delenex.