Schematic of clinical trial design. (A) Proposed model of the effects of decitabine, NY-ESO-1 vaccination (CDX-1401), and nivolumab in patients in the study. (1) Decitabine induces expression of NY-ESO-1 in patient blasts. (2) cDCs take up CDX-1401 through the DEC-205 receptor, process it, and present the full-length NY-ESO-1 protein as an antigen. Poly-ICLC activates DCs and induces expression of costimulatory molecules such as CD80. DCs activate T cells through interactions between antigen-bound HLA and the TCR and costimulatory molecules (such as CD80-CD28). (3) Administration of nivolumab leads to reinvigoration of NY-ESO-1–specific T cells. (4) These reinvigorated T cells cause cytotoxicity of NY-ESO-1–expressing blasts. Both CD8⁺ and CD4⁺ T cells are hypothesized to play a role in the immunologic response to therapy; for simplicity, the figure shown here focuses on the CD8⁺ T-cell response. (B) Schematic diagram showing the treatment schedule of decitabine, vaccine, and nivolumab. Initial responses to treatment were assessed during the DLT window. Throughout the study, serial peripheral blood, bone marrow, and plasma samples were collected. Poly(I:C), polyinosinic-polycytidylic acid; TCR, T-cell receptor.