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Ipilimumab + decitabine is a combination therapy investigated for the treatment of relapsed or refractory myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Ipilimumab is a recombinant human monoclonal antibody that acts as an immune checkpoint inhibitor by binding to the Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4). By blocking CTLA-4, it prevents the inhibitory signal that normally downregulates T-cell activation, thereby enhancing the immune system's ability to attack tumor cells. Decitabine is a small molecule hypomethylating agent that functions as a DNA methyltransferase inhibitor. It incorporates into DNA and covalently binds to DNA methyltransferases, leading to their depletion and subsequent global DNA hypomethylation. This process can reactivate tumor suppressor genes that were silenced by hypermethylation. The combination is designed to leverage the epigenetic priming effects of decitabine to enhance the efficacy of CTLA-4 blockade in myeloid malignancies.
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