Vaccine Educated T cells and a CD123 Bi-Specific T-Cell Engager for Treatment of Acute Myeloid Leukemia
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ABSTRACT: Immunotherapy strategies in acute myeloid leukemia remain limited. CD123 is a promising target as it is overexpressed in myeloid blasts. This preclinical work investigates possible synergy of CD123 T cell engager and dendritic cell based vaccine, which can induce the expansion of leukemia specific T cells. Efficacy of combination therapy was evaluated in a patient-derived xenograft model and the infused T cells were later collected for single cell rnaseq to determine effects on gene expression pathways and clonality. In the present study, we demonstrated that the combination of DC/AML fusion vaccine and a CD123 T cell engager SAR440234 led to an increase in tumor specific T cell immunity and enhanced anti-leukemia effect in vitro. Furthermore, the combination treatment was shown to increase cytotoxic T cell subsets and clonotypic expansion and eradicate disease in vivo. Thus the combination of T cell engager and vaccination or adoptive T cell transfer is a novel approach that merits further investigation in clinical trials.
ORGANISM(S): Homo sapiens
PROVIDER: GSE265780 | GEO | 2025/06/06
REPOSITORIES: GEO
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