Abstract 6556: Model characterization and tumor immune profile assessment of syngeneic Renca murine renal cell carcinoma in female BALB/c

Abstract Renal cell carcinoma (RCC) affects over 80, 000 people in the U.S. annually, leading to ∼15, 000 deaths. Although immuno-oncology therapies can yield responses for some patients, complete remissions are rare. This limitation highlights the importance of new therapeutic approaches, necessitating effective animal models for preclinical testing. Syngeneic models, which allow for functional immune systems capable of influencing tumor growth and metastases, are valuable for studying immune responses and immunosuppressive factors. One such model is Renca, derived from a spontaneous renal cortical adenocarcinoma in a BALB/c mouse. Renca is relevant because it varies in immunogenicity and mirrors human RCC in many aspects. This model is a promising tool in immuno-oncology, enabling the testing of new treatments, alone and in combination with other therapies. To ensure reproducible growth, a well-established tumor was collected and processed. The resulting cells where then implanted subcutaneously at two inocula (1.0E+06 and 5.0E+05 cells), with and without dietgel, to observe known weight loss characteristics of the model. Renca demonstrated aggressive growth, with a median tumor volume doubling time of ∼3 days, a median time to 2000 mm3 of ∼30 days, disease related mortality of 12.5-25% with dietgel and 37.5%-62.5% without dietgel and disease associated body weight change ranging from -5.1 to 0% with dietgel and -15.1 to -14.6% without dietgel. The baseline tumor immunophenotype in vehicle control treated animals was measured by flow cytometry and revealed myeloid-derived suppressor cells to be the dominant subset in the tumor. With G-MDSCs and M-MDSCs representing 31.5% and 16% of total CD45+ cells, respectively. In addition, tumors were poorly infiltrated with lymphocyte subsets as CD8+ T cells and NK cells each represented less than 0.25% of the CD45+ cell compartment. Furthermore, checkpoint inhibitors including PD-1, TIM-3, and LAG-3 were highly expressed on the T cells present (90.0%, 80.5%, and 74.7% positive respectively), suggesting an immunosuppressed state. Next, response to standard of care (SoC), checkpoint inhibitors, and radiation were evaluated. All treatments had limited impact on tumor regression, but focal beam radiation showed the most significant effect by extending the time to progression. Checkpoint inhibitors were minimal effective, while SoC treatment produced a moderate response. In summary, the Renca model has proven to be a reliable syngeneic tumor model for RCC research. Its immunosuppressive microenvironment is valuable for studying combination therapies that could potentially convert non-immunogenic tumors into more immunogenic tumors, enhancing treatment responsiveness. Future studies will focus on optimizing orthotopic implantation and sampling tumors at varying sizes, which has been shown to impact TIL populations. Citation Format: Justin Snider, Lauren Kucharczyk, Anita Zaitouna, Sheri Barnes, David Draper, Scott Wise. Model characterization and tumor immune profile assessment of syngeneic Renca murine renal cell carcinoma in female BALB/c [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 6556.