Efficacy and engraftment of anti-CD19 CAR-T cells in murine lupus 4343

Abstract Description CAR-T cells have emerged as a therapeutic strategy for autoimmune diseases, including systemic lupus erythematosus (SLE). One open question is the impact of preconditioning on therapeutic responses. In preliminary experiments using pre-irradiated lupus-prone New Zealand Black/New Zealand White (NZB/W) mice, second-generation anti-mCD19 CAR-T cells positively impacted many disease features. Significant bone marrow (BM) B-cell depletion and lower proteinuria were observed across irradiated groups, suggesting an immunosuppressive effect. Based on these findings, we aimed to demonstrate the impact of CAR-T cells over irradiation on various immunologic and clinical features by modifying the conditioning regimen in these mice. Twenty two-week-old pre-irradiated mice were treated with PBS or CAR-T cells+IL-2. Lymphocytes were assessed in blood, BM, and spleen 4-weeks post treatment. The engraftment of CAR-T cells was documented in all samples. CAR-T cell-treated mice showed persistent B cell decrease in various subsets (marginal zone/naïve B cells and plasma cells). Furthermore, increases in CD4+ and CD8+ T cells, with a lower percentage of effector/central memory T cells and higher naïve T cells were observed as an outcome of CAR-T treatment. CAR-T treated mice also displayed lower anti-dsDNA antibodies and proteinuria. Thus, CAR-T cells showed a differential impact on lupus beyond irradiation. Other disease features to ascertain CAR-T cell efficacy for SLE are being explored. Funding Sources Supported by Kyverna Therapeutics, Inc., Emeryville, CA. Topic Categories Therapeutic Approaches to Autoimmunity (THER)