pepinemab + pembrolizumab

Pepinemab + pembrolizumab is a combination of two monoclonal antibody immunotherapies under investigation for the treatment of advanced, recurrent, or metastatic head and neck squamous cell carcinoma (HNSCC) and other cancers. Pepinemab is a humanized IgG4 monoclonal antibody that targets semaphorin 4D (SEMA4D), a protein involved in immune regulation within the tumor microenvironment. By blocking SEMA4D, pepinemab promotes infiltration and activation of dendritic cells and CD8+ T-cells while reversing immunosuppression in tumors[2][6][7]. Pembrolizumab (Keytruda) is an anti–PD-1 immune checkpoint inhibitor that blocks the programmed cell death protein 1 (PD-1) on T-cells, enhancing immune-mediated tumor cell killing[1][5]. The rationale for combining these agents is to enhance antitumor immunity by both reversing myeloid-derived suppressor cell–mediated immunosuppression (via SEMA4D blockade) and unleashing T-cell activity against cancer cells (via PD-1 inhibition)[3][4][7].