Investigating the effect of invariant natural killer T cell receptor on T cell development and function from human pluripotent stem cells 4127

Abstract Description Invariant Natural Killer T (iNKT) cells are a subset of unconventional T cells that recognize lipid antigens independent of HLA molecules. This ability to bypass donor-recipient matching, along with their rapid cytokine production, makes them an attractive immunotherapy agent. However, their low frequency in vivo makes investigating their functions difficult. Efforts have been made to scale up “iNKT-like” cell production by manipulating iNKT T cell receptor (iTCR) expression in stem cells. However, their use of xenogeneic feeder cells and non-chemically defined systems make understanding their developmental niche and clinical translation difficult. To investigate if iTCR expression during T cell development affects its developmental trajectory, we turn to combine our lab’s expertise in niche and genetic engineering. Using our feeder-free and chemically defined differentiation protocol, we can robustly generate mature conventional T cells from human pluripotent stem cells (hPSCs). By integrating a functional iTCR into hPSCs through CRISPR/Cas gene editing, we generated different subsets of iTCR expressing mature T cells that express the innate transcription factor PLZF. Further comparison with other engineered hPSC-derived T cells will help elucidate how iTCR expression and signaling regulate iNKT cell development. Ultimately, we aim to harness specific properties of unconventional T cells to develop more effective off-the-shelf T cell therapeutics for various diseases. Topic Categories Hematopoiesis and Immune System Development (HEM)