Abstract 4014: Humanized mouse model to assess PBMC donor derived autologous CD19 CAR Ts for efficacy against Raji tumors and related cytokine release

Abstract

Abstract Immuno-oncology cell therapies engage the immune system to treat cancer. In recent years, adoptive T-cell therapy with CD19-specific chimeric antigen receptors (CARs) has shown promise for treatment of various malignancies, including acute lymphoblastic leukemia. However, CAR-T-cell therapies have been hampered by various adverse events, including cytokine release syndrome (CRS). To predict and minimize CRS effects from CAR-T therapies, a human immune preclinical murine model that combines efficacy and toxicity readouts is essential. Here, we describe the development of PBMC humanized mouse model based on the NSG-MHC I/II-DKO strain to study autologous CD19 CAR-T treatment related tumor growth inhibition and CRS in vivo. Three different PBMC donors were used to generate CAR-T (CD28-Cd3z) directed against a CD19 epitome. Our preliminary data demonstrate that CD19 CAR-T treatment stimulated dynamic and PBMC donor dependent cytokine release with IFN-g, IL-10, IL-4, IL-2, IL-6 and TNF. Our model showed elevation of shared proinflammatory cytokines (IFN-g, IL-10, IL-2 and TNF) observed in humans after CD19 CAR-T treatment. Currently, we are evaluating our PBMC based cytokine release model in CD19 CAR-T cells tumor control study. Our results to date indicate that PBMC-engrafted NSG-MHC I/II-DKO mouse models are vital platforms to screen adoptive T-cell therapy for potential CRS. Citation Format: Senthil Ramalingam, Danying Cai, Lindsay Shopland, James G. Keck. Humanized mouse model to assess PBMC donor derived autologous CD19 CAR Ts for efficacy against Raji tumors and related cytokine release [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4014.