Abstract 2792: Characterization of spontaneous in vivo cachexia models in Champions TumorGraft™ models.

Abstract

Abstract Cachexia, defined as a loss of adipose tissue and skeletal muscle mass not reversible by nutritional support, is present in the majority of patients with advanced cancer progression. This reduces the patient's quality of life and impacts their ability to function normally and undergo treatments. Reversing cachexia has been problematic due to a lack of quality pre-clinical models. Traditional xenograft models using cell lines are limited due to their inability to accurately replicate the whole body response to cancer. Champions Oncology overcomes this challenge through the use of its innovative Champions TumorGraft™ platform, where primary human tumors are implanted into immunocompromised mice in a manner that preserves the biological properties of the original human tumor. Champions has identified a panel of three TumorGraft models which spontaneously induce cachexia when implanted subcutaneously into nude mice: 1) CTG-0282, a pancreatic cancer model, 2) CTG-0765, a NSCLC model, and 3) CTG-0804, a renal cell carcinoma model. All three models have shown a greater than 90% cachexia rate, as demonstrated by lost body weight, over multiple passages. In addition, loss of body weight correlates with an increase in tumor volume size. Mice that have little or no tumor growth show no loss of body weight. Past studies have indicated a function for pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6) and interferon gamma (IFNγ), in the cachexia process. Champions is currently investigating the roles of these possible tumor-mediated factors in the aforementioned models. Principle among these factors is IL-6, which has been shown to be required in the regulation of cachexia in tumor-bearing mice and is correlated with weight loss and survival in patients. Preliminary results from our studies suggest a correlation between IL-6 levels and spontaneous cachexia in Champions TumorGraft models. In summary, we demonstrate that the Champions TumorGraft platform preserves the biological properties of the original human tumor, including spontaneous cachexia behavior in these models, and is therefore ideal for oncology drug development programs focused on the inhibition of cachexia. Citation Format: Nathan Anderson, Tin Oo Khor, Andrew Feldhaus, Katie Olson, John Latham, David Sidransky, Elizabeth M. Bruckheimer. Characterization of spontaneous in vivo cachexia models in Champions TumorGraft™ models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2792. doi:10.1158/1538-7445.AM2013-2792