CD19 CAR T cells with chimeric inhibitory receptor

CD19 CAR T cells with chimeric inhibitory receptor is an experimental, self-regulating CAR T cell therapy designed to treat B-cell malignancies, such as acute lymphoblastic leukemia (ALL) and lymphoma, while mitigating severe toxicities like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The construct co-expresses a standard CD19-targeted CAR (with either CD28 or 4-1BB costimulatory domains) alongside a novel chimeric inhibitory receptor (CIR). This CIR consists of an anti-IFN-gamma scFv extracellular domain coupled to the intracellular inhibitory signaling domain of TIGIT. In the presence of high levels of IFN-gamma—a key driver of CRS—the CIR triggers inhibitory signaling within the CAR T cell to temporarily attenuate its activation and cytokine production. Preclinical studies indicate that this auto-regulating mechanism reduces the secretion of pro-inflammatory mediators and improves metabolic fitness and resistance to exhaustion without compromising anti-tumor efficacy.

Other names

auto-regulating CD19 CAR T cellsself-regulating CD19 CAR T cells