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Title: | Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive |
Authors: | 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 |
Keywords: | cell therapy;chimeric antigen receptor;IL-10;regulatory T cell;suppression |
Issue Date: | 28-Jul-2021 |
Publisher: | Wiley-VCH |
Citation: | Mohseni, Y.R. et al. (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), pp. 2522 - 2530. doi: 10.1002/eji.202048934. |
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. |
Description: | Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. Supporting Information is available online at: https://onlinelibrary.wiley.com/doi/10.1002/eji.202048934#support-information-section . |
URI: | https://bura.brunel.ac.uk/handle/2438/29193 |
DOI: | https://doi.org/10.1002/eji.202048934 |
ISSN: | 0014-2980 |
Other Identifiers: | ORCiD: Cristiano Scottá https://orcid.org/0000-0003-3942-5201 ORCiD: Fadi Issa https://orcid.org/0000-0002-8279-7732 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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