Abstract 807: A novel immunodeficient rat for modeling human cancer

Abstract

Abstract Animal models of human cancer offer the potential to study human tumor growth kinetics, genetic variance among human cancers, and provide in vivo platforms for drug efficacy testing. In particular, immunodeficient mouse models have been invaluable in modeling a wide range of human cancers. However, some cancer lines don’t grow well in the available mouse models or show variability in growth kinetics from mouse to mouse, making drug efficacy studies difficult due to differences in tumor size at the onset of treatment. These challenges are also seen in patient derived xenograft (PDX) models, in addition to long timeframes to obtain sufficient mice with PDX tissue growth for drug efficacy studies. Mice are also limited in tumor growth potential with regard to humane endpoints and small size also limits the volume of blood that can be collected for analysis. An immunodeficient rat model could provide a solution to some of these issues. A rat model would allow for larger tumor size, easier surgical manipulation, and greater volume of tissue and blood sampling for downstream analysis. In addition, large tumors from rats could be serially transplanted into mice for drug efficacy testing and could provide a large number of transplanted mice in a shorter period of time compared with serially transplanting from mouse to mouse. We have created an immunodeficient rat model with a functional deletion of the Rag2 gene. This knockout, created using spermatogonial stem cells, lacks mature B and T cells. To assess the capability of the Rag2 knockout rat to accept human xenografts, we transplanted 2 commercially available human cancer cell lines into our animals. The human REH acute lymphocytic leukemia cell line was transplanted via intravenous injection and the human glioblastoma cell line U87MG was transplanted subcutaneously. Both cell lines survived in the Rag2 knockout rat and resulted in the growth of tumors comprised of human cells. Studies are underway to characterize the Rag2 knockout rat’s ability to grow other human cell lines, including those that do not grow well in mice, and PDX tissues. Citation Format: Fallon K. Noto, Angela Arey, Christopher McClain, Wei Zhang, Tseten Yeshi. A novel immunodeficient rat for modeling human cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 807. doi:10.1158/1538-7445.AM2017-807