Morris, JamesZarin, PayamMilaszewski, Madison2026-01-1320252026-01-072026Milaszewski, Madison. 2026. Characterization and Optimization of a Murine Engineered CAR T cell Surrogate for the Treatment of Autoimmune and Autoinflammatory Conditions . Masters Thesis, Harvard University Division of Continuing Education.32403886https://dash.harvard.edu/handle/1/42725035The adaptive immune system can occasionally generate cells that are autoreactive, leading them to trigger autoimmune responses led by diminishing function or numbers of Tregs. Regulatory T cells (Tregs) are a rare subpopulation of T cells that play a critical role in the maintenance of homeostasis and immune tolerance. While Chimeric Antigen Receptor (CAR) T cell therapy is already an important therapeutic modality for tackling complex autoimmune conditions, the generation of a CAR Treg may prove more effective and specific, treating the autoimmune condition more directly without the off target toxicity effects. This thesis evaluates preclinical surrogates for CD19 CAR T cells which, following optimization, were compared to CD19 CAR Tregs in a murine inflammatory model in terms of safety, engraftment, off-target effects, and efficacy. Following optimization, the newly engineered CAR T cell was an effective control tested in co-culture assays with B cells and T cells, showcasing the off-target immune response that was not observed with the specific CAR Treg cultures. In an in vivo model of systemic lupus erythematosus, CAR T cells generated a significant immune response compared to the CAR Tregs. This suggests that a specific CAR Treg would be a safer alternative to a CAR T cell-based therapy.application/pdfenBiologyThesis or Dissertation2026-01-130009-0000-8132-6691