Authors: Abigail Cheever, Chloe Kang, Hunter Lindsay, Mackenzie Hansen, Kim O'Neill, K Scott Weber
Mentors: K Scott Weber, Kim O'Neill
Insitution: Brigham Young University
Chimeric Antigen Receptor (CAR) T cell therapy is a modern technology that has become a widely accepted treatment for blood cancers such as lymphoma and leukemia. Recent studies have proven the successful application of CAR T cell therapies in autoimmune diseases as well. Graves’ Disease (GD) is an autoimmune disease that affects approximately 1 in 100 Americans and is the most common cause of hyperthyroidism. GD is mediated by anti-thyroid stimulating hormone receptor (TSHR) antibodies produced by autoreactive B cells. Our hypothesis is that a curative treatment for GD can be created by designing a CAR T cell that specifically targets the autoreactive B cells in GD, by using TSHR as a binding domain to act as bait for the anti-TSHR B cells. We selected TSHR epitopes for the binding domain of the CAAR T cell, and our anti-TSHR antibodies bound significantly to our engineered CAAR T cells. A target B cell line with anti-TSHR B cell receptors was engineered using the Nalm6 B cell line. Using primary human CAAR T cells, activation and cytotoxicity assays against anti-TSHR B cells shows that CAAR T cell therapy is an effective and promising method to treat antibody mediated autoimmune diseases like GD.