Abstract 51: The SRG immunodeficient rat demonstrates utility across multiple tumor types of different organ origins
Authors: Yong Koh Meng Aw , Eberle Christoph , Dowdy Christopher , Walton Grace , Begemann Diane , Brenzel Christopher , Noto Fallon , Festin Stephen 
Published: April 2023

Introduction The number of approved cancer drugs as well as those in development have doubled over the last decade. With this increase comes a need for validated immunodeficient animal models that allow engraftment of tumor xenografts, an important role in the drug development process. Immunodeficient rats are suited for studies that require serial tissue sampling such as blood. Under NIH guidelines, up to 88µl of whole blood from a 125g rat can be collected per day compared to 21µl of blood from a 30g mouse. Tumor size endpoints in rats are also larger at 40mm in diameter compared to 20mm in mice, contingent on other humane endpoints. This allows researchers to follow drug response or toxicology within the same animal over more frequent time intervals. The SRG is an immunodeficient rat with deletions in the recombination activating gene 2 (Rag2) and interleukin 2 receptor gamma (Il2r-γ) that results in impaired V(D)J recombination and lymphocyte maturation respectively, ensuring T, B and NK cells deficiency. In this study, we set out to examine the levels of monocytes, another key component of the immune system response as well as for immunophenotypic differences between male and female SRGs, which have not been done in previous studies. We further evaluated the growth kinetics of 20 human tumor cell lines from 12 different cancer types in the SRG.

Methods Whole blood was collected from 20 SRG rats of each gender (n=40) with 2 CD (Sprague Dawley) rats of each gender used as control group (n=4). PBMCs were isolated and analyzed by flow cytometry for CD4 and CD8 positive T cells, B cells, NK cells and monocytes. Tumor cell lines were inoculated subcutaneously into individual SRGs and tumor measurements obtained at regular intervals until study or humane endpoints.

Results While levels of circulating T, B and NK cells in SRGs were reduced compared to WT CD rats (p&lt;0.05), no statistically significant difference was observed in monocyte subpopulation (p&gt;0.05). There was also no significant difference in T, B, NK cells as well as monocyte levels between male and female SRGs (p&gt;0.05). All 20 human tumor cell lines tested in the SRG engrafted successfully and demonstrated good growth kinetics with some tumors growing more than 10,000mm3 in size.

Conclusion The immunodeficient SRG has demonstrated utility in supporting the engraftment of human tumor xenografts across 12 different cancer types. An area of interest for future studies would be on the role of monocytes on humanization.

Citation Format: Koh Meng Aw Yong, Christoph Eberle, Christopher Dowdy, Grace Walton, Diane Begemann, Christopher Brenzel, Fallon Noto, Stephen Festin. The SRG immunodeficient rat demonstrates utility across multiple tumor types of different organ origins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 51.