Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia

Nat Biotechnol. 2023 Nov;41(11):1618-1632. doi: 10.1038/s41587-023-01684-0. Epub 2023 Mar 13.


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 vitro and in vivo efficacy in cell line- and human-derived AML models with minimal off-target toxicity toward relevant healthy human tissues. This provides a strong rationale for further clinical development.

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Humans
  • Immunotherapy, Adoptive
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / metabolism
  • Leukemia, Myeloid, Acute* / therapy
  • T-Lymphocytes
  • Transcriptome* / genetics