論文 - 詳細
| RRC ID | 73846 |
|---|---|
| 著者 | Gottschlich A, Thomas M, Grünmeier R, Lesch S, Rohrbacher L, Igl V, Briukhovetska D, Benmebarek MR, Vick B, Dede S, Müller K, Xu T, Dhoqina D, Märkl F, Robinson S, Sendelhofert A, Schulz H, Umut Ö, Kavaka V, Tsiverioti CA, Carlini E, Nandi S, Strzalkowski T, Lorenzini T, Stock S, Müller PJ, Dörr J, Seifert M, Cadilha BL, Brabenec R, Röder N, Rataj F, Nüesch M, Modemann F, Wellbrock J, Fiedler W, Kellner C, Beltrán E, Herold T, Paquet D, Jeremias I, von Baumgarten L, Endres S, Subklewe M, Marr C, Kobold S. |
| タイトル | Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia. |
| ジャーナル | Nat Biotechnol |
| Abstract |
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. |
| 公開日 | 2023-3-13 |
| DOI | 10.1038/s41587-023-01684-0 |
| PII | 10.1038/s41587-023-01684-0 |
| PMID | 36914885 |
| IF | 36.553 |
| リソース情報 | |
| ヒト・動物細胞 | AFS98(RCB4486) |