SENTI-401

SENTI-401 is an allogeneic logic-gated and multi-armed CAR-NK (chimeric antigen receptor natural killer) cell therapy developed by Senti Biosciences for the treatment of CEA-expressing solid tumors, particularly colorectal cancer. The therapy incorporates a NOT GATE gene circuit that pairs a CEA-targeting activating-CAR (aCAR) with an inhibitory-CAR (iCAR) that recognizes VSIG2, a safety antigen uniquely expressed in certain healthy gastrointestinal and lung epithelial cells. This design allows SENTI-401 to target and kill CEA-expressing tumor cells while preventing the killing of CEA-expressing healthy epithelial cells, thereby reducing the risk of on-target, off-tumor toxicities. The therapy is also multi-armed with constitutively active IL-15 (crIL-15) and IL-21 to enhance NK cell function, serial killing capacity, and durable anti-tumor activity. SENTI-401 utilizes Senti Bio's proprietary Gene Circuit platform, including the Bioinformatics-Driven Antigen Pairing (B-DAP) discovery platform for identifying safety antigens and the Design-Build-Test-and-Learn (DBTL) platform for optimizing CAR constructs[1][3][12].