Abstract 6508: The SRG RAT, an immunodeficient model for immortalized cell line and primary patient derived orthotopic glioblastoma xenograft tumors

Abstract Human cancer xenografts are vital for understanding tumor biology, growth kinetics, and therapeutic efficacy. Historically, immunodeficient mice have been the standard rodent species for cancer xenografts. However, an immunodeficient rat that supports a variety of human cancer cell types would provide a larger rodent for easier surgical manipulation, serial blood sampling, and combined efficacy, pharmacokinetics, and toxicology studies. Hera BioLabs created a Sprague Dawley Rag2 -/-, Il2rg -/- Rat (SRG RAT®) that provides a highly supportive environment for growing tumors of human origin. The SRG rat lacks B, T, and NK cells and is more immunodeficient than the Nude rat, suggesting it may be permissive to a wider variety of human cancer types. Here we demonstrate the utility of the SRG rat in supporting intracranial growth of cell- and patient-derived (CDX and PDX) human cancers that grow in the brain. We inoculated female SRG rats with human primary glioblastoma cell lines U87MG-luc and U118MG-luc to establish tumors in the striatum of the rat brain. Additionally, PDX models from both glioblastoma stem cells and adherent, differentiated glioblastoma cells from different human tumors in the brain were isolated, briefly cultured, and inoculated into the striatum of male and female SRG rats. Preliminary biomarker analyses including Ki67, p53, IDH1, and Map2 indicate clinically relevant gene expression. Through a multifaceted approach including in-life bioluminescent imaging, MRI data, and post-mortem histology, we demonstrate robust tumor growth in the brains of SRG rats when established from human glioblastoma CDX, glioblastoma stem cell PDX tumors and differentiated glioblastoma PDX tumors. These data confirm that the SRG rat is an excellent host for studying subtypes of glioblastoma with several clinically relevant markers. These data demonstrate that the SRG rat has a high utility for studies requiring intracranial orthotopic tumor implantation due to its larger size, permissiveness to human xenografts, and ability to support a higher tumor burden when compared to mice. As the most immunodeficient rat commercially available, the SRG RAT supports preclinical testing of brain cancer therapeutics in a larger rodent strain relative to commercially available mouse models. Citation Format: Diane Begemann, Elizabeth Fenton, Niveen Fulcher, Cynthia Dunn, Darrell Robertson, Cassandra Scutchfield, Tanner Keener, Cleusa De Oliveira, John Kelly, Ying Xia, John Ronald, R. Grace Walton, Shilpa Sampathi, Valeriya Steffey, Michael J. Schlosser, Susanne Schmid, Matthew O. Hebb, Fallon K. Noto. The SRG RAT, an immunodeficient model for immortalized cell line and primary patient derived orthotopic glioblastoma xenograft tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6508.