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Reddy, N.R.* ; Maachi, H. ; Xiao, Y.* ; Simic, M.S.* ; Yu, W.* ; Tonai, Y.* ; Cabanillas, D.A.* ; Serrano-Wu, E.* ; Pauerstein, P.T.* ; Tamaki, W.* ; Allen, G.M.* ; Parent, A.V.* ; Hebrok, M. ; Lim, W.A.*

Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs.

Science 386:eadl4793 (2024)
Verlagsversion DOI PMC
Closed
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Immune homeostasis requires a balance of inflammatory and suppressive activities. To design cells potentially useful for local immune suppression, we engineered conventional CD4+ T cells with synthetic Notch (synNotch) receptors driving antigen-triggered production of anti-inflammatory payloads. Screening a diverse library of suppression programs, we observed the strongest suppression of cytotoxic T cell attack by the production of both anti-inflammatory factors (interleukin-10, transforming growth factor-β1, programmed death ligand 1) and sinks for proinflammatory cytokines (interleukin-2 receptor subunit CD25). Engineered cells with bespoke regulatory programs protected tissues from immune attack without systemic suppression. Synthetic suppressor T cells protected transplanted beta cell organoids from cytotoxic T cells. They also protected specific tissues from unwanted chimeric antigen receptor (CAR) T cell cross-reaction. Synthetic suppressor T cells are a customizable platform to potentially treat autoimmune diseases, organ rejection, and CAR T cell toxicities with spatial precision.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Immune Cells; Immunotherapy; Recognition; Challenges; Cancer
ISSN (print) / ISBN 0036-8075
e-ISSN 1095-9203
Zeitschrift Science
Quellenangaben Band: 386, Heft: 6726, Seiten: , Artikelnummer: eadl4793 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort 1200 New York Ave, Nw, Washington, Dc 20005 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Diabetes und Organoid Technology (IDOT)
Förderungen Valhalla Foundation
NIH/NIDDK
NIH/NCI