Aeolus Pharmaceuticals, Inc. (OTC Bulletin Board: AOLS) announced today the initiation of a study to test the anti-tumor effects of AEOL 10150 when combined with radiation and chemotherapy in nude mice bearing human non-small cell lung cancer (NSCLC) xenografts. This study, led by Zeljko Vujaskovic, M.D. Ph.D. of Duke University, is designed to build on the growing body of pre-clinical data that shows that AEOL 10150 protects healthy tissue from radiation damage, while not interfering with the effectiveness of radiotherapy in killing tumors. AEOL 10150 has also been shown to be an effective treatment for damage to the lungs due to exposure to radiation.
While previous studies have shown that AEOL 10150 synthetic can suppress both acute and late normal tissue radiation injury, it is not known what effect this compound might have on tumor chemoresponsivness or responsiveness to combination chemo/radiation therapy. There is convincing evidence in the literature to support the hypothesis that Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) are capable of promoting tumor vascular angiogenesis and that antioxidants have antiangiogenic activity. Additional data suggests that antiangiogenic compounds act synergistically with radiotherapy by increasing radiation damage to the vasculature, leading to secondary tumor cell kill, thus raising the possibility that AEOL 10150 may improve chemotherapeutic and/or radiotherapeutic control of tumors through an antivascular mechanism.
“This study will provide important insight into AEOL 10150’s ability to protect healthy tissue from combination chemo and radiation therapy, while either enhancing or not hindering the effect of this therapy on the tumor cells,” stated John L. McManus, President and Chief Executive Officer of Aeolus Pharmaceuticals, Inc. “Successful completion of this study will allow us to amend our IND with the US FDA, so that we can run phase 1 and phase 2 studies in non-small cell lung cancer patients to support our cancer radiation therapy as well as provide further safety data to support our program for the compound as a countermeasure for Pulmonary Acute Radiation Syndrome.”
Animal Model and Design
In this experiment, nude mice will be injected with human NSCLC tumor cells. Animals will be irradiated using a clinically relevant fractionated radiation schedule, and the chemotherapy group will be receiving paclitaxel intraperitonealy once a week for a total of three weeks. Tumor size will be measured twice weekly, and statistical analysis will be performed on data collected from the tumor growth assay. Tumor growth delay experiments will be conducted to test the efficacy of each treatment regimen, and the endpoint used is the number of days to reach 5 times the original tumor volume. At the time of sacrifice, tumors will be harvested for tissue homogenization and molecular analysis or immunohistochemical analysis. Endpoints to be assessed include HIF-1 alpha, a pro-angiogenic transcription factor, and its downstream gene product, vascular endothelial growth factor (VEGF), which regulates vessel sprouting and tubal formation. The endothelial cell marker CD31 will be used to evaluate overall microvessel density and a ratio of immature vasculature versus total vascularization will be measured by positive CD105 expression against CD31.