Dataset Information

CAR T cell therapy becomes CHIC: "cytokine help intensified CAR" T cells.

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 CD3ζ 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.

SUBMITTER: Thomas S

PROVIDER: S-EPMC9869021 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CAR T cell therapy becomes CHIC: "cytokine help intensified CAR" T cells.

Thomas Simone S Abken Hinrich H

Frontiers in immunology 20230109

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 CD3ζ 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. ...[more]

PMID: 36700225

Similar Datasets

Project description:The successful treatment of patients affected by B-cell malignancies with Chimeric Antigen Receptor (CAR)-T cells represented a breakthrough in the field of adoptive cell therapy (ACT). However, CAR-T therapy is not an option for every patient, and several needs remain unmet. In particular, the production of CAR-T cells is expensive, labor-intensive and logistically challenging; additionally, the toxicities deriving from CAR-T cells infusion, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), have been documented extensively. Alternative cellular therapy products such as Cytokine-induced killer (CIK) cells have the potential to overcome some of these obstacles. CIK cells are a heterogeneous population of polyclonal CD3+CD56+ T cells with phenotypic and functional properties of NK cells. CIK cell cytotoxicity is exerted in a major histocompatibility complex (MHC)-unrestricted manner through the engagement of natural killer group 2 member D (NKG2D) molecules, against a wide range of hematological and solid tumors without the need for prior antigen exposure or priming. The foremost potential of CIK cells lies in the very limited ability to induce graft-versus-host disease (GvHD) reactions in the allogeneic setting. CIK cells are produced with a simple and extremely efficient expansion protocol, which leads to a massive expansion of effector cells and requires a lower financial commitment compared to CAR-T cells. Indeed, CAR-T manufacturing involves the engineering with expensive GMP-grade viral vectors in centralized manufacturing facilities, whereas CIK cell production is successfully performed in local academic GMP facilities, and CIK cell treatment is now licensed in many countries. Moreover, the toxicities observed for CAR-T cells are not present in CIK cell-treated patients, thus further reducing the costs associated with hospitalization and post-infusion monitoring of patients, and ultimately encouraging the delivery of cell therapies in the outpatient setting. This review aims to give an overview of the limitations of CAR-T cell therapy and outline how the use of CIK cells could overcome such drawbacks thanks to their unique features. We highlight the undeniable advantages of using CIK cells as a therapeutic product, underlying the opportunity for further research on the topic.

Dataset Information

CAR T cell therapy becomes CHIC: "cytokine help intensified CAR" T cells.

Publications

CAR T cell therapy becomes CHIC: "cytokine help intensified CAR" T cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets