Vaccine-educated T cells and a CD123 bispecific T-cell engager for treatment of acute myeloid leukemia.

abstractT-cell engager (TCE) therapy has demonstrated significant therapeutic efficacy in patients with hematologic malignancies. Durable responses have been linked with T-cell clonotypic expansion. We hypothesized that combining vaccine-educated T cells (veTcs) that induce the expansion of leukemia-specific T cells would enhance efficacy of TCE through greater induction of tumor-specific immunity. In this study, we explored a TCE targeting human CD123 on myeloid leukemia cells in conjunction with T cells stimulated by an autologous dendritic cell/acute myeloid leukemia fusion vaccine in a murine xenograft model. We demonstrated that the combination of CD123 TCE (SAR440234) and veTcs boosted tumor-specific T-cell immunity and enhanced antileukemia effect in vitro. Furthermore, in vivo SAR440234 and veTca combination treatment fully eradicated leukemia engraftment outperforming SAR440234 in conjunction with uneducated T cells. This effect was associated with an increase in cytotoxic T-cell subsets and clonotypic expansion. Thus, the combination of TCE with adoptive T-cell transfer of veTcs is a novel approach that merits further investigation in clinical trials.