REV-403

REV-403 is a preclinical-stage T-cell engager (TCE) developed by Revitope Oncology for the treatment of solid tumors, including lung cancer. It is the lead internal candidate utilizing the proprietary TwoGATE (Two-component Gated Activation for Tumor Eradication) platform. The therapeutic system consists of two separate bispecific antibodies that target the epidermal growth factor receptor (EGFR) and programmed death-ligand 1 (PD-L1), respectively. Each antibody carries half of a 'silent' T-cell engaging domain (a split paratope for CD3). Functional T-cell engagement occurs only when both components bind simultaneously to their respective antigens on the surface of the same tumor cell and are activated by tumor-specific proteases. This 'AND-gate' logic is designed to restrict T-cell activity to the tumor microenvironment, thereby minimizing on-target, off-tumor toxicities and widening the therapeutic window compared to conventional bispecific antibodies. As of late 2024, REV-403 was advancing toward GLP toxicology studies.