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GentiBio's allogeneic HLA knockout engineered regulatory T cells (EngTregs) are an off-the-shelf cell therapy candidate designed for the treatment of autoimmune and inflammatory diseases. To enable long-term persistence and avoid immune rejection, these cells are engineered with a human leukocyte antigen (HLA) knockout to prevent T-cell mediated clearance. To specifically address natural killer (NK) cell-mediated "missing-self" rejection, the cells express a membrane-anchored, synthetic NKG2A-specific engager. This engager selectively inhibits NKG2A+ NK cells without activating NKG2C+ subsets, overcoming a key limitation of traditional HLA-E based strategies. The platform also incorporates FOXP3 stabilization and antigen-specific receptors via a dual-AAV knock-in system to maintain a stable regulatory phenotype and targeted function.
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