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**Zalifrelimab + gemcitabine** is an investigational combination therapy consisting of zalifrelimab, a fully human IgG1 monoclonal antibody targeting cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4), and gemcitabine, a nucleoside analog chemotherapeutic agent. Zalifrelimab acts as an immune checkpoint inhibitor, blocking CTLA-4 to promote T cell activation and reduce regulatory T cell suppression, thereby enhancing antitumor immune responses. Gemcitabine inhibits DNA synthesis via incorporation into DNA strands, resulting in cell cycle arrest and apoptosis. Additionally, gemcitabine can modulate the tumor immune microenvironment, including suppression of regulatory T cells and myeloid-derived suppressor cells (MDSCs), and is under investigation as an immune modulator in combination with checkpoint inhibitor therapy. The combination is being explored in preclinical and early clinical settings as a strategy to enhance the efficacy of immunotherapy, particularly in immune-cold or chemotherapy-refractory tumors[3][4].
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