Vaccine-Educated T cells and a CD123 Bispecific T-Cell Engager for Treatment of Acute Myeloid Leukemia Open Access

• Adoptive T cell therapy utilizing ex-vivo vaccine priming enhances efficacy of CD123 T cell engager in acute myeloid leukemia

• Vaccine educated T cells could enhance the effect of T cell engagers via increased tumor specific immunity and T cell clonotype expansion.

T 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 (veTc) that induce the expansion of leukemia specific T cells would enhance efficacy of TCE through greater induction of tumor specific immunity. In the present study, we explored a TCE targeting human CD123 on myeloid leukemia cells in conjunction with T cells stimulated by an autologous DC/AML fusion vaccine in a murine xenograft model. We demonstrated that the combination of CD123 T cell engager (SAR440234) and veTc boosted tumor specific T cell immunity and enhanced anti-leukemia effect in vitro. Furthermore, in vivo SAR440234 and veTc 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 T cell engager with adoptive T cell transfer of vaccine educated T cells is a novel approach that merits further investigation in clinical trials.