biostudies-literatureGottschlich AEuropean Research Council1618-1632https://www.ebi.ac.uk/biostudies/studies/S-EPMC7615296biostudies-literatureUnknown41(11)Chimeric antigen receptor T cells (CAR-T cells) have emerged as a powerful treatment option for individuals with B cell malignancies but have yet to achieve success in treating acute myeloid leukemia (AML) due to a lack of safe targets. Here we leveraged an atlas of publicly available RNA-sequencing data of over 500,000 single cells from 15 individuals with AML and tissue from 9 healthy individuals for prediction of target antigens that are expressed on malignant cells but lacking on healthy cells, including T cells. Aided by this high-resolution, single-cell expression approach, we computationally identify colony-stimulating factor 1 receptor and cluster of differentiation 86 as targets for CAR-T cell therapy in AML. Functional validation of these established CAR-T cells shows robust in vNature biotechnologySingle-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia.PMC7615296756017101100460Muller KRataj FEndres SUmut OWellbrock JSendelhofert APaquet DHerold TTsiverioti CAKellner CBriukhovetska DStock SRohrbacher LGrunmeier RDorr JJeremias IBenmebarek MRIgl VDede SThomas MLorenzini TCadilha BLSchulz HNuesch MCarlini ENandi SRoder NStrzalkowski TFiedler WLesch SModemann FMarr CSubklewe MKobold SRobinson SVick BMuller PJSeifert MDhoqina DGottschlich AKavaka Vvon Baumgarten LXu TMarkl FBeltran EBrabenec RfalseSingle-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia.Chimeric antigen receptor T cells (CAR-T cells) have emerged as a powerful treatment option for individuals with B cell malignancies but have yet to achieve success in treating acute myeloid leukemia (AML) due to a lack of safe targets. Here we leveraged an atlas of publicly available RNA-sequencing data of over 500,000 single cells from 15 individuals with AML and tissue from 9 healthy individuals for prediction of target antigens that are expressed on malignant cells but lacking on healthy cells, including T cells. Aided by this high-resolution, single-cell expression approach, we computationally identify colony-stimulating factor 1 receptor and cluster of differentiation 86 as targets for CAR-T cell therapy in AML. Functional validation of these established CAR-T cells shows robust in v2023-01-01T00:00:00Z2023 Nov2026-05-29T08:39:49.475Z2024-11-05T16:53:21.939ZS-EPMC76152963691488510.1038/s41587-023-01684-0