CD93 CAR T cells with VE-cadherin iCAR

CD93 CAR T cells with VE-cadherin iCAR are an experimental, genetically engineered chimeric antigen receptor T‑cell product designed to target CD93-expressing acute myeloid leukemia (AML) cells while limiting on-target, off-tumor toxicity to vascular endothelium. CD93 is highly expressed on many AML blasts but is also present on human endothelial cells, creating a risk of endothelial damage for conventional CD93 CAR T cells.[3][11] To mitigate this, a NOT-gate inhibitory CAR (iCAR) specific for VE-cadherin (vascular endothelial cadherin, an endothelial junctional protein absent from AML blasts but expressed on endothelial cells) is co-expressed; engagement of VE-cadherin delivers an inhibitory signal that suppresses CD93 CAR activation on healthy endothelium while preserving cytotoxic activity against VE-cadherin–negative, CD93-positive AML cells.[3] This dual-receptor logic design is being explored preclinically as a cell therapy for AML within academic translational research programs.