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

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

In: NAT BIOTECHNOL, Vol. 41, No. 11, 11.2023, p. 1618-1632.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Gottschlich, A, Thomas, M, Grünmeier, R, Lesch, S, Rohrbacher, L, Igl, V, Briukhovetska, D, Benmebarek, M-R, 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 2023, 'Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia', NAT BIOTECHNOL, vol. 41, no. 11, pp. 1618-1632. https://doi.org/10.1038/s41587-023-01684-0

APA

Gottschlich, A., Thomas, M., Grünmeier, R., Lesch, S., Rohrbacher, L., Igl, V., Briukhovetska, D., Benmebarek, M-R., Vick, B., Dede, S., Müller, K., Xu, T., Dhoqina, D., Märkl, F., Robinson, S., Sendelhofert, A., Schulz, H., Umut, Ö., Kavaka, V., ... Kobold, S. (2023). Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia. NAT BIOTECHNOL, 41(11), 1618-1632. https://doi.org/10.1038/s41587-023-01684-0

Vancouver

Gottschlich A, Thomas M, Grünmeier R, Lesch S, Rohrbacher L, Igl V et al. 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. https://doi.org/10.1038/s41587-023-01684-0

Bibtex

@article{e11e66917e1e48ad84e182f2fe73f598,
title = "Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia",
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.",
author = "Adrian Gottschlich and Moritz Thomas and Ruth Gr{\"u}nmeier and Stefanie Lesch and Lisa Rohrbacher and Veronika Igl and Daria Briukhovetska and Mohamed-Reda Benmebarek and Binje Vick and Sertac Dede and Katharina M{\"u}ller and Tao Xu and Dario Dhoqina and Florian M{\"a}rkl and Sophie Robinson and Andrea Sendelhofert and Heiko Schulz and {\"O}yk{\"u} Umut and Vladyslav Kavaka and Tsiverioti, {Christina Angeliki} and Emanuele Carlini and Sayantan Nandi and Thadd{\"a}us Strzalkowski and Theo Lorenzini and Sophia Stock and M{\"u}ller, {Philipp Jie} and Janina D{\"o}rr and Matthias Seifert and Cadilha, {Bruno L} and Ruben Brabenec and Natalie R{\"o}der and Felicitas Rataj and Manuel N{\"u}esch and Franziska Modemann and Jasmin Wellbrock and Walter Fiedler and Christian Kellner and Eduardo Beltr{\'a}n and Tobias Herold and Dominik Paquet and Irmela Jeremias and {von Baumgarten}, Louisa and Stefan Endres and Marion Subklewe and Carsten Marr and Sebastian Kobold",
note = "{\textcopyright} 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2023",
month = nov,
doi = "10.1038/s41587-023-01684-0",
language = "English",
volume = "41",
pages = "1618--1632",
journal = "NAT BIOTECHNOL",
issn = "1087-0156",
publisher = "NATURE PUBLISHING GROUP",
number = "11",

}

RIS

TY - JOUR

T1 - Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia

AU - Gottschlich, Adrian

AU - Thomas, Moritz

AU - Grünmeier, Ruth

AU - Lesch, Stefanie

AU - Rohrbacher, Lisa

AU - Igl, Veronika

AU - Briukhovetska, Daria

AU - Benmebarek, Mohamed-Reda

AU - Vick, Binje

AU - Dede, Sertac

AU - Müller, Katharina

AU - Xu, Tao

AU - Dhoqina, Dario

AU - Märkl, Florian

AU - Robinson, Sophie

AU - Sendelhofert, Andrea

AU - Schulz, Heiko

AU - Umut, Öykü

AU - Kavaka, Vladyslav

AU - Tsiverioti, Christina Angeliki

AU - Carlini, Emanuele

AU - Nandi, Sayantan

AU - Strzalkowski, Thaddäus

AU - Lorenzini, Theo

AU - Stock, Sophia

AU - Müller, Philipp Jie

AU - Dörr, Janina

AU - Seifert, Matthias

AU - Cadilha, Bruno L

AU - Brabenec, Ruben

AU - Röder, Natalie

AU - Rataj, Felicitas

AU - Nüesch, Manuel

AU - Modemann, Franziska

AU - Wellbrock, Jasmin

AU - Fiedler, Walter

AU - Kellner, Christian

AU - Beltrán, Eduardo

AU - Herold, Tobias

AU - Paquet, Dominik

AU - Jeremias, Irmela

AU - von Baumgarten, Louisa

AU - Endres, Stefan

AU - Subklewe, Marion

AU - Marr, Carsten

AU - Kobold, Sebastian

N1 - © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

PY - 2023/11

Y1 - 2023/11

N2 - 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.

AB - 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.

U2 - 10.1038/s41587-023-01684-0

DO - 10.1038/s41587-023-01684-0

M3 - SCORING: Journal article

C2 - 36914885

VL - 41

SP - 1618

EP - 1632

JO - NAT BIOTECHNOL

JF - NAT BIOTECHNOL

SN - 1087-0156

IS - 11

ER -