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This combination therapy consists of four agents: - **Ivonescimab (AK112)**, a bispecific monoclonal antibody targeting PD-1 and VEGF-A, which acts as an immune checkpoint inhibitor and anti-angiogenic agent. - **Ligufalimab (AK117)**, a humanized monoclonal antibody targeting CD47, which blocks the CD47-SIRPα pathway to enhance macrophage-mediated phagocytosis of tumors with reduced hematotoxicity. - **Cisplatin**, a classic platinum-based chemotherapeutic that causes DNA crosslinking and apoptosis in tumor cells. - **5-Fluorouracil**, an antimetabolite chemotherapeutic that inhibits thymidylate synthase, leading to inhibition of DNA synthesis and tumor cell death. This combination is being studied in multiple advanced malignancies, including head and neck squamous cell carcinoma and other gastrointestinal cancers, aiming to synergize direct cytotoxicity (cisplatin, 5-FU) with innate/adaptive immune activation (AK112, AK117)[1][2][3][4][5].
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