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Gottschlich, Adrian; Thomas, Moritz; Grünmeier, Ruth; Lesch, Stefanie; Rohrbacher, Lisa; Igl, Veronika; Briukhovetska, Daria; Benmebarek, Mohamed-Reda; Vick, Binje; Dede, Sertac; Müller, Katharina; Xu, Tao; Dhoqina, Dario; Märkl, Florian; Robinson, Sophie; Sendelhofert, Andrea; Schulz, Heiko; Umut, Öykü; Kavaka, Vladyslav; Tsiverioti, Christina Angeliki; Carlini, Emanuele; Nandi, Sayantan; Strzalkowski, Thaddäus; Lorenzini, Theo; Stock, Sophia; Müller, Philipp Jie; Dörr, Janina; Seifert, Matthias; Cadilha, Bruno L; Brabenec, Ruben; Röder, Natalie; Rataj, Felicitas; Nüesch, Manuel; Modemann, Franziska; Wellbrock, Jasmin; Fiedler, Walter; Kellner, Christian; Beltrán, Eduardo; Herold, Tobias; Paquet, Dominik; Jeremias, Irmela; von Baumgarten, Louisa; Endres, Stefan; Subklewe, Marion; Marr, Carsten; Kobold, Sebastian
Nature biotechnology, 11/2023, Volume: 41, Issue: 11Journal Article
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.
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