Reshmi Parameswaran, MS, PhD, member of Case CCC's Immune Oncology Program, was awarded a two-year, $200,000 Established Investigator Grant by the National Scleroderma Foundation. The funding supports her research using BAFF CAR-T treatment for systemic sclerosis.
Systemic scleroderma (SSc) is a rare autoimmune disease that affects an estimated 125,000 Americans. SSc is considered the most fatal rheumatic disease, characterized by fibrosis of the skin and lungs as well as vascular changes. B cells have emerged as drivers of pathogenesis and indicators for disease severity in SSc including the inflammatory cytokine IL-6 and the presence of autoantibodies (AA) in 95% of advanced patients. Indeed, therapies targeting B cells and the B cell activating factor (BAFF) signaling axis including anti-CD20 and antiBAFF have shown promising results in reducing the severity of disease in B cell-associated autoimmunity, but these treatments are not curative
Parameswaran's lab seeks to circumvent these issues using a BAFF-ligand-based CAR T cell product. The BAFF family receptors BAFFR, TACI, and BCMA are highly expressed in B cells at different proportions depending on their maturation state, including plasma cells. Researchers in her lab hypothesize that elimination of autoreactive B cells will reduce fibrosis and collagen deposition in a model of SSc. The goal is to improve outcomes in SSc by advancing this technology to IND-enabling studies.