The use of STVTs is a novel approach to eradicating cancer. NuVas's hypothesis is that STVTs cause a thromboetical occlusion of the tumor vessels, whereby nutrients and oxygen are prevented from reaching the dependent tumor cells resulting in ischemic apoptosis and infarctive necrosis of the tumor. To better evaluate the vascular effects the STVTs exert on the tumor microvascular system, we propose to use a non- invasive in vivo and in situ fluorescence microscopic technique. This technique will allow us to make repeated observation of microtumors over periods up to 2 - 3 weeks, and thus make it possible to analyze the dynamics of phenomena that affect the tumor microvascular system and to measure the tumor size in response to intravenous administration of STVTs. We believe that direct observation of the vascular system, with components of the tumor and the normal system in the same observation field, is one of the best ways to facilitate the design and production of optimal STVT molecules. The intravital microscopy system can quantitatively and qualitatively provide important information about the direct biochemical and physiological effects of STVT molecules on individual microvessels in normal and tumor tissues. To achieve these goals, a collaboration between Dr. Borgstrom's group at Sidney Kimmel Cancer Center, San Diego and NuVas has been started. Dr. Borgstrom's group has developed a system for non-invasive, in vivo and in situ study of tumor vasculature in awake mice using video- microscopy (1). Their in vivo system is based on the dorsal skinfold chamber technique in mice and utilizes (i) green fluorescence protein (GFP) to label tumor cells to allow continuous measurement of tumor size, and (ii) RITC-dextran as a plasma enhancer to allow quantification of tumor micro-vascular phenomena. To further improve the technique to also allow direct and continuous evaluation of mitotic and apoptotic indices in vivo, we propose to implement cancer cell lines stably transfected with the H2B-GFP fusion protein. PROPOSED COMMERCIAL APPLICATION: It is clear that the need for better anti-cancer agents still exists. The development of novel STVTs to treat cancer will help some proportion of the 1.5 million people in the US who develop cancer each year. This is more than a 410 billion market.
