Abstract 3293: Activity and safety of an antiangiogenic peptide in spontaneous head and neck squamous cell carcinoma in cats

Abstract

Abstract Anginex is a rationally designed, synthetic peptide that inhibits proliferation of human and mouse endothelial cells and demonstrates anti-tumor activity in murine tumor models. The anti-tumor and anti-angiogenic activity of Anginex is attributable, at least in part, to its interaction with galectin-1, a carbohydrate binding protein. As an intermediate step in the clinical translation of Anginex and related anti-vascular agents, we are investigating the effects of Anginex in spontaneous feline head and neck squamous cell carcinoma (HNSCC). Feline HNSCC shares morphology, clinical behavior, and biologic features such as intratumoral hypoxia and expression of EGFR, COX-2, and mutant p53 with its human counterpart. Our objectives were to investigate the activity of Anginex in feline cells and provide evidence of its safety in a phase I trial in cats with HNSCC. To establish Anginex activity in vitro, we evaluated the effect of 24 hour exposure to Anginex doses ranging from 2.5 – 25 uM on proliferation of both feline aortic endothelial cells (FAECs) and feline HNSCC cells (SCCF1) using flow cytometry and labeling with propidium iodide and bromodeoxyuridine (BrdU). With increasing Anginex dose, we observed accumulation of FAECs in G1 and decreased uptake of BrdU. We observed no effect in SCCF1 cells. To investigate safety, cats were treated with Anginex in cohorts of at least three animals at doses of 1, 3, and 9 mg/kg daily for 5 days. Clinical, laboratory and histologic features were evaluated before and after treatment. There were no serious adverse events during treatment. Continuous variables including body weight and laboratory variables were compared before and after treatment using a Wilcoxon signed rank test. No statistically significant changes occurred in these parameters. These data indicate that Aniginex is active against feline endothelial cells specifically and appears to be safe in cats. We are currently investigating the effects of Anginex on tumor physiology and in combination with radiation therapy for feline HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3293. doi:10.1158/1538-7445.AM2011-3293