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Thomas, Simone ; Abken, Hinrich

CAR T cell therapy becomes CHIC: “cytokine help intensified CAR” T cells

Thomas, Simone und Abken, Hinrich (2023) CAR T cell therapy becomes CHIC: “cytokine help intensified CAR” T cells. Frontiers in Immunology 13.

Veröffentlichungsdatum dieses Volltextes: 24 Mrz 2023 07:49
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.53986


Zusammenfassung

Chimeric antigen receptors (CARs) in the canonical "second generation" format provide two signals for inducing T cell effector functions; the primary "signal-1" is provided through the TCR CD3 zeta chain and the "signal-2" through a linked costimulatory domain to augment activation. While therapy with second generation CAR T cells can induce remissions of leukemia/lymphoma in a spectacular ...

Chimeric antigen receptors (CARs) in the canonical "second generation" format provide two signals for inducing T cell effector functions; the primary "signal-1" is provided through the TCR CD3 zeta chain and the "signal-2" through a linked costimulatory domain to augment activation. While therapy with second generation CAR T cells can induce remissions of leukemia/lymphoma in a spectacular fashion, CAR T cell persistence is frequently limited which is thought to be due to timely limited activation. Following the "three-signal" dogma for inducing a sustained T cell response, cytokines were supplemented to provide "signal-3" to CAR T cells. Recent progress in the understanding of structural biology and receptor signaling has allowed to engineer cytokines for more selective, fine-tuned stimulation of CAR T cells including an artificial autocrine loop of a transgenic cytokine, a cytokine anchored to the CAR T cell membrane or inserted into the extracellular CAR domain, and a cytokine receptor signaling moiety co-expressed with the CAR or inserted into the CAR endodomain. Here we discuss the recent strategies and options for engineering such "cytokine help intensified CAR" (CHIC) T cells for use in adoptive cell therapy.



Beteiligte Einrichtungen


Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftFrontiers in Immunology
Verlag:FRONTIERS MEDIA SA
Ort der Veröffentlichung:LAUSANNE
Band:13
Datum9 Januar 2023
InstitutionenMedizin > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Leibniz-Institut für Immuntherapie (LIT)
Identifikationsnummer
WertTyp
10.3389/fimmu.2022.1090959DOI
Stichwörter / KeywordsCLONAL EXPANSION; ANTIGEN; IL-15; LYMPHOCYTES; EXPRESSION; RECEPTORS; SUPERIOR; PROMOTES; SURVIVAL; GROWTH; cytokine; signal-3; T cell activation; chimeric antigen receptor; adoptive cell immunotherapy
Dewey-Dezimal-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenJa
URN der UB Regensburgurn:nbn:de:bvb:355-epub-539866
Dokumenten-ID53986

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