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Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive

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Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive. / Mohseni, Yasmin R.; Saleem, Adeel; Tung, Sim L. et al.

In: European Journal of Immunology, Vol. 51, No. 10, 10.2021, p. 2522-2530.

Research output: Contribution to journalArticlepeer-review

Harvard

Mohseni, YR, Saleem, A, Tung, SL, Dudreuilh, C, Lang, C, Peng, Q, Volpe, A, Adigbli, G, Cross, A, Hester, J, Farzaneh, F, Scotta, C, Lechler, RI, Issa, F, Fruhwirth, GO & Lombardi, G 2021, 'Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive', European Journal of Immunology, vol. 51, no. 10, pp. 2522-2530. https://doi.org/10.1002/eji.202048934

APA

Mohseni, Y. R., Saleem, A., Tung, S. L., Dudreuilh, C., Lang, C., Peng, Q., Volpe, A., Adigbli, G., Cross, A., Hester, J., Farzaneh, F., Scotta, C., Lechler, R. I., Issa, F., Fruhwirth, G. O., & Lombardi, G. (2021). Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive. European Journal of Immunology, 51(10), 2522-2530. https://doi.org/10.1002/eji.202048934

Vancouver

Mohseni YR, Saleem A, Tung SL, Dudreuilh C, Lang C, Peng Q et al. Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive. European Journal of Immunology. 2021 Oct;51(10):2522-2530. https://doi.org/10.1002/eji.202048934

Author

Mohseni, Yasmin R. ; Saleem, Adeel ; Tung, Sim L. et al. / Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive. In: European Journal of Immunology. 2021 ; Vol. 51, No. 10. pp. 2522-2530.

Bibtex Download

@article{b60553cc358c4293aa98302634f69fa6,
title = "Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive",
abstract = "Clinical trials of Treg therapy in transplantation are currently entering phases IIa and IIb, with the majority of these employing polyclonal Treg populations that harbor a broad specificity. Enhancing Treg specificity is possible with the use of chimeric antigen receptors (CARs), which can be customized to respond to a specific human leukocyte antigen (HLA). In this study, we build on our previous work in the development of HLA-A2 CAR-Tregs by further equipping cells with the constitutive expression of interleukin 10 (IL-10) and an imaging reporter as additional payloads. Cells were engineered to express combinations of these domains and assessed for phenotype and function. Cells expressing the full construct maintained a stable phenotype after transduction, were specifically activated by HLA-A2, and suppressed alloresponses potently. The addition of IL-10 provided an additional advantage to suppressive capacity. This study therefore provides an important proof-of-principle for this cell engineering approach for next-generation Treg therapy in transplantation.",
keywords = "Cell therapy, Chimeric antigen receptor, IL-10, Regulatory T cell, Suppression",
author = "Mohseni, {Yasmin R.} and Adeel Saleem and Tung, {Sim L.} and Caroline Dudreuilh and Cameron Lang and Qi Peng and Alessia Volpe and George Adigbli and Amy Cross and Joanna Hester and Farzin Farzaneh and Cristiano Scotta and Lechler, {Robert I.} and Fadi Issa and Fruhwirth, {Gilbert O.} and Giovanna Lombardi",
note = "Funding Information: We thank Dr. Kate Milward (University of Oxford) for the pCAG.IL-10.eGFP plasmid, Dr. Marc Martinez-Llordella for the B-LCLs, and Dr. Carlo Scala/Miss Kholood Basahel (all King's College London) for technical help with lentivirus production. The authors received funding from the Medical Research Council (MRC Centre for Transplantation at KCL: MR/J006742/1), the British Heart Foundation (TG/16/2/32657 to GL), and Cancer Research UK (C48390/A21153 to GF). CD was funded by Societe Francophone de Transplantation and the European Society of Organ Transplantation. FI is a Wellcome Trust CRCD Fellow. This work was further supported by the Department of Health via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre award to King's Health Partners, and the Wellcome/EPSRC Centre for Medical Engineering (WT203148/Z/16/Z). This work was further supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas? NHS Foundation Trust and King's College London and the NIHR Clinical Research Facility. Views expressed are those of the authors and not necessarily those of the NHS, NIHR, or DoH. Funding Information: We thank Dr. Kate Milward (University of Oxford) for the pCAG.IL‐10.eGFP plasmid, Dr. Marc Martinez‐Llordella for the B‐LCLs, and Dr. Carlo Scala/Miss Kholood Basahel (all King's College London) for technical help with lentivirus production. The authors received funding from the Medical Research Council (MRC Centre for Transplantation at KCL: MR/J006742/1), the British Heart Foundation (TG/16/2/32657 to GL), and Cancer Research UK (C48390/A21153 to GF). CD was funded by Societe Francophone de Transplantation and the European Society of Organ Transplantation. FI is a Wellcome Trust CRCD Fellow. This work was further supported by the Department of Health via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre award to King's Health Partners, and the Wellcome/EPSRC Centre for Medical Engineering (WT203148/Z/16/Z). This work was further supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas{\textquoteright} NHS Foundation Trust and King's College London and the NIHR Clinical Research Facility. Views expressed are those of the authors and not necessarily those of the NHS, NIHR, or DoH. Publisher Copyright: {\textcopyright} 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.",
year = "2021",
month = oct,
doi = "10.1002/eji.202048934",
language = "English",
volume = "51",
pages = "2522--2530",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "10",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive

AU - Mohseni, Yasmin R.

AU - Saleem, Adeel

AU - Tung, Sim L.

AU - Dudreuilh, Caroline

AU - Lang, Cameron

AU - Peng, Qi

AU - Volpe, Alessia

AU - Adigbli, George

AU - Cross, Amy

AU - Hester, Joanna

AU - Farzaneh, Farzin

AU - Scotta, Cristiano

AU - Lechler, Robert I.

AU - Issa, Fadi

AU - Fruhwirth, Gilbert O.

AU - Lombardi, Giovanna

N1 - Funding Information: We thank Dr. Kate Milward (University of Oxford) for the pCAG.IL-10.eGFP plasmid, Dr. Marc Martinez-Llordella for the B-LCLs, and Dr. Carlo Scala/Miss Kholood Basahel (all King's College London) for technical help with lentivirus production. The authors received funding from the Medical Research Council (MRC Centre for Transplantation at KCL: MR/J006742/1), the British Heart Foundation (TG/16/2/32657 to GL), and Cancer Research UK (C48390/A21153 to GF). CD was funded by Societe Francophone de Transplantation and the European Society of Organ Transplantation. FI is a Wellcome Trust CRCD Fellow. This work was further supported by the Department of Health via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre award to King's Health Partners, and the Wellcome/EPSRC Centre for Medical Engineering (WT203148/Z/16/Z). This work was further supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas? NHS Foundation Trust and King's College London and the NIHR Clinical Research Facility. Views expressed are those of the authors and not necessarily those of the NHS, NIHR, or DoH. Funding Information: We thank Dr. Kate Milward (University of Oxford) for the pCAG.IL‐10.eGFP plasmid, Dr. Marc Martinez‐Llordella for the B‐LCLs, and Dr. Carlo Scala/Miss Kholood Basahel (all King's College London) for technical help with lentivirus production. The authors received funding from the Medical Research Council (MRC Centre for Transplantation at KCL: MR/J006742/1), the British Heart Foundation (TG/16/2/32657 to GL), and Cancer Research UK (C48390/A21153 to GF). CD was funded by Societe Francophone de Transplantation and the European Society of Organ Transplantation. FI is a Wellcome Trust CRCD Fellow. This work was further supported by the Department of Health via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre award to King's Health Partners, and the Wellcome/EPSRC Centre for Medical Engineering (WT203148/Z/16/Z). This work was further supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas’ NHS Foundation Trust and King's College London and the NIHR Clinical Research Facility. Views expressed are those of the authors and not necessarily those of the NHS, NIHR, or DoH. Publisher Copyright: © 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.

PY - 2021/10

Y1 - 2021/10

N2 - Clinical trials of Treg therapy in transplantation are currently entering phases IIa and IIb, with the majority of these employing polyclonal Treg populations that harbor a broad specificity. Enhancing Treg specificity is possible with the use of chimeric antigen receptors (CARs), which can be customized to respond to a specific human leukocyte antigen (HLA). In this study, we build on our previous work in the development of HLA-A2 CAR-Tregs by further equipping cells with the constitutive expression of interleukin 10 (IL-10) and an imaging reporter as additional payloads. Cells were engineered to express combinations of these domains and assessed for phenotype and function. Cells expressing the full construct maintained a stable phenotype after transduction, were specifically activated by HLA-A2, and suppressed alloresponses potently. The addition of IL-10 provided an additional advantage to suppressive capacity. This study therefore provides an important proof-of-principle for this cell engineering approach for next-generation Treg therapy in transplantation.

AB - Clinical trials of Treg therapy in transplantation are currently entering phases IIa and IIb, with the majority of these employing polyclonal Treg populations that harbor a broad specificity. Enhancing Treg specificity is possible with the use of chimeric antigen receptors (CARs), which can be customized to respond to a specific human leukocyte antigen (HLA). In this study, we build on our previous work in the development of HLA-A2 CAR-Tregs by further equipping cells with the constitutive expression of interleukin 10 (IL-10) and an imaging reporter as additional payloads. Cells were engineered to express combinations of these domains and assessed for phenotype and function. Cells expressing the full construct maintained a stable phenotype after transduction, were specifically activated by HLA-A2, and suppressed alloresponses potently. The addition of IL-10 provided an additional advantage to suppressive capacity. This study therefore provides an important proof-of-principle for this cell engineering approach for next-generation Treg therapy in transplantation.

KW - Cell therapy

KW - Chimeric antigen receptor

KW - IL-10

KW - Regulatory T cell

KW - Suppression

UR - http://www.scopus.com/inward/record.url?scp=85112109428&partnerID=8YFLogxK

U2 - 10.1002/eji.202048934

DO - 10.1002/eji.202048934

M3 - Article

AN - SCOPUS:85112109428

VL - 51

SP - 2522

EP - 2530

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 10

ER -

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