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Belrestotug (GSK5733584) is a humanized IgG1 monoclonal antibody that targets CD96 (also known as Tactile), an inhibitory immune checkpoint receptor expressed on T cells and natural killer (NK) cells. CD96 belongs to the immunoglobulin superfamily and competes with the activating receptor CD226 (DNAM-1) for binding to the ligand CD155 (PVR). By binding to CD96, belrestotug blocks its inhibitory signaling, thereby promoting the activation and anti-tumor effector functions of immune cells. Developed by GSK, belrestotug is currently being evaluated in the Phase 2 I-SPY 2 platform trial, managed by the QuantumLeap Healthcare Collaborative, for the neoadjuvant treatment of high-risk, early-stage breast cancer. In this trial context, it is investigated both as a monotherapy and in combination with the PD-1 inhibitor dostarlimab to enhance therapeutic response.
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