Vaccine-educated T cells and a CD123 bispecific T-cell engager for treatment of acute myeloid leukemia
Year: 2025
Type: article
Abstract: ABSTRACT: 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 (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.
Source: Blood Advances
Authors: Jessica Liegel, Dina Stroopinsky, Giulia Cheloni, Dimitra Karagkouni, Myrna Nahas, Yuling Ma, Daniela Torres, Isabella Saldarriaga, Shuoshuo Wang, Antonella Arruda de Amaral, Athanasios Ploumakis, John Clohessy, Joseph Abirached, Lina Bisharat, Paula Fraenkel, Ozlem Yildirim, Hélène Bonnevaux, Stephane Guerif, Katie Rallis, Georges Chedid, Donald Kufe, Ioannis S. Vlachos, David Avigan, Jacalyn Rosenblatt
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W4413137980