SynNotch T cells

SynNotch T cells are primary murine T cells engineered via retroviral transduction with a synthetic Notch (SynNotch) receptor-based circuit. This circuit is designed to recognize the inflammation-associated protein VCAM1, which is minimally expressed in healthy kidneys but strongly upregulated in inflammatory conditions like crescentic glomerulonephritis (cGN). Upon binding to VCAM1, the SynNotch circuit activates a downstream synthetic transcriptional program that drives the expression and secretion of immunosuppressive molecules, specifically IL-10, and surface expression of PD-L1. This localized immune regulation aims to minimize off-target toxicity associated with broad systemic immunosuppression, offering a novel therapeutic approach for kidney autoimmunity. The functionality of these cells has been validated in vitro, and their persistence and systemic distribution demonstrated in Rag1 -/- mice.