Publications by authors named "Michelle Seaberg"
Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell-Related Autoimmune Diseases.
Arthritis Rheumatol
July 2023
Objective: Dysregulated APRIL/BAFF signaling is implicated in the pathogenesis of multiple autoimmune diseases, including systemic lupus erythematosus and lupus nephritis. We undertook this study to develop and evaluate a high-affinity APRIL/BAFF antagonist to overcome the clinical limitations of existing B cell inhibitors.
Methods: A variant of TACI-Fc generated by directed evolution showed enhanced binding for both APRIL and BAFF and was designated povetacicept (ALPN-303).
Article Synopsis
- The study focuses on the role of T cell activation in systemic sclerosis (SSc), a disease marked by fibrosis in skin and lungs, and evaluates the dual ICOS/CD28 antagonist, acazicolcept (ALPN-101), in mouse models resembling SSc.
- Acazicolcept was administered to two different SSc mouse models over six weeks, showing good tolerance and significant improvements in skin and lung fibrosis markers, including reduced dermal thickness and collagen content.
- The treatment also altered T cell populations in the spleen and lungs, indicating a potential therapeutic strategy for managing SSc by targeting immune activation.
Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). CD146 and CCR5 are proteins that mark activated T helper 17 (Th17) cells. The Th17 cell phenotype is promoted by the interaction of the receptor ICOS on T cells with ICOS ligand (ICOSL) on dendritic cells (DCs).
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