Thomas, Simone and Abken, Hinrich (2023) CAR T cell therapy becomes CHIC: "cytokine help intensified CAR" T cells. FRONTIERS IN IMMUNOLOGY, 13: 1090959. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CLONAL EXPANSION; ANTIGEN; IL-15; LYMPHOCYTES; EXPRESSION; RECEPTORS; SUPERIOR; PROMOTES; SURVIVAL; GROWTH; cytokine; signal-3; T cell activation; chimeric antigen receptor; adoptive cell immunotherapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Mar 2024 15:04 |
| Last Modified: | 07 Mar 2024 15:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58946 |
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