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

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.

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Publication Details

Journal
Blood Advances
Published
2025-08-14
DOI
https://doi.org/10.1182/bloodadvances.2024015449
Citations
1
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
1.05

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article

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

Özlem Yıldırım, Dimitra Karagkouni, Athanasios Ploumakis, Ioannis S. Vlachos et al.
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Blood Advances
CAR-T cell therapy research
1.05
article

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

Özlem Yıldırım, Dimitra Karagkouni, Athanasios Ploumakis, Ioannis S. Vlachos, John G. Clohessy, Shuoshuo Wang, Hélène Bonnevaux, David Avigan, Jacalyn Rosenblatt, Paula G. Fraenkel, Yuling Ma, Myrna Nahas, Katie Rallis, Georges Chedid, Giulia Cheloni, Lina Bisharat, Isabella Saldarriaga, Joseph Abirached, Antonella Arruda de amaral, Dina Stroopinsky, S. Guérif, Daniela Torres, D Kufe, Jessica J. Liegel
article en
1 citations

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.

Blood AdvancesVol. 9(21)
Beth Israel Deaconess Medical Center (US), Harvard University (US), Beth Israel Deaconess Hospital (US), Sanofi (France) (FR), Sanofi (United States) (US), Dana-Farber Cancer Institute (US)
Sanofi, Beth Israel Deaconess Medical Center, Celgene, Massachusetts Life Sciences Center, Harvard Stem Cell Institute, Kite Pharma, Pharmacyclics, National Heart, Lung, and Blood Institute, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 19%
CAR-T cell therapy research
1.05
DOIOpen Access PDFOpenAlex
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