Preconditioning determines engraftment and therapeutic efficacy of anti-CD19 CAR-T cells in murine lupus - PubMed
3 hours ago
- #CAR-T cells
- #preconditioning
- #lupus nephritis
- Anti-CD19 CAR-T cells are a promising therapy for autoimmune diseases like systemic lupus erythematosus.
- The study investigates how preconditioning (irradiation intensity) affects CAR-T cell engraftment and therapeutic efficacy in murine lupus models.
- High-dose irradiation alone can improve lupus disease, making it hard to separate CAR-T-specific effects from irradiation effects.
- Low-dose irradiation fails to support durable CAR-T cell engraftment.
- Intermediate-dose irradiation achieves consistent CAR-T cell engraftment in lymphoid organs while minimizing irradiation-driven disease modulation.
- Under intermediate-dose conditions, CAR-T cell treatment significantly depletes B cells (naïve, marginal zone, plasma cells) and reduces anti-dsDNA antibodies, preventing renal disease progression.
- This provides a preclinical framework for reduced-intensity lymphodepletion strategies in human CAR-T therapy for autoimmune diseases.