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CBP501 + cisplatin + nivolumab is a **triple combination therapy** under investigation for cancer treatment. - **CBP501** is a calmodulin-binding peptide that enhances platinum uptake into cancer cells. It acts primarily by inhibiting the G2 checkpoint through binding to proteins such as 14-3-3, Chk1, Chk2, and mitogen-activated protein kinases, leading to increased accumulation of cancer cells in the G2-M phase and potentiation of cisplatin cytotoxicity. CBP501 also blocks calmodulin and suppresses macrophage-driven cytokine production and interaction with cancer cells, which reduces metastasis and cancer stem cell-like phenotypes[1][3][5]. - **Cisplatin** is a platinum-based chemotherapy agent that induces DNA crosslinking damage and cancer cell death[5]. - **Nivolumab** is a fully human monoclonal antibody targeting PD-1 on T cells, functioning as an immune checkpoint inhibitor. By blocking PD-1, nivolumab prevents interaction with its ligands, restoring T-cell activity and enabling anti-tumor immune response[2][4]. The combination is designed to increase **immunogenic cell death (ICD)** and synergistically upregulate immune response, with CBP501 and cisplatin enhancing tumor cell death and ICD markers, while nivolumab further boosts anti-tumor immunity by reactivating cytotoxic T cells. Preclinical studies show this combination increases tumor infiltration of CD8+ T cells and downregulates immunosuppressive macrophages, yielding greater tumor regression[5].
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