Pepinemab (also known as VX-15/SA-4F) is an investigational, humanized monoclonal antibody that targets semaphorin 4D (SEMA4D, CD100), a transmembrane protein involved in immune regulation and neuronal guidance. SEMA4D is expressed on activated T cells, B cells, and dendritic cells, and its receptor plexin-B1 is found on endothelial cells, neurons, and immune cells. By binding to SEMA4D, pepinemab blocks its signaling, thereby inhibiting the negative regulatory effects of SEMA4D on immune cell infiltration and activation in the tumor microenvironment. This promotes the recruitment and function of cytotoxic T cells and reduces immunosuppressive cells. It is being developed as an immuno-oncology agent for the treatment of advanced solid tumors, including head and neck squamous cell carcinoma (HNSCC) and glioblastoma.