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Constitutive expression of interleukin-27 diminishes proinflammatory cytokine production without impairing effector function of engineered T cells.
- Source :
-
Cytotherapy [Cytotherapy] 2023 Sep; Vol. 25 (9), pp. 913-919. Date of Electronic Publication: 2023 Jun 10. - Publication Year :
- 2023
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Abstract
- Immunomodulatory cytokines can alter the tumor microenvironment and promote tumor eradication. Interleukin (IL)-27 is a pleiotropic cytokine that has potential to augment anti-tumor immunity while also facilitating anti-myeloma activity. We engineered human T cells to express a recombinant single-chain (sc)IL-27 and a synthetic antigen receptor targeting the myeloma antigen, B-cell maturation antigen, and evaluated the anti-tumor function of T cells bearing scIL-27 in vitro and in vivo. We discovered that T cells bearing scIL-27 sustained anti-tumor immunity and cytotoxicity yet manifested a profound reduction in pro-inflammatory cytokines granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha. IL-27-expressing T cells therefore present a potential avenue to avert treatment-related toxicities commonly associated with engineered T-cell therapy due to the reduced pro-inflammatory cytokine profile.<br />Competing Interests: Declaration of Competing Interest Christopher L. Baker:Paid through a sponsored research agreement with Triumvira Immunologics. Jonathan L. Bramson: Co-founder of Triumvira Immunologics. Shareholder in Triumvira Immunologics. Paid Consultant for Triumvira Immunologics. Co-inventor on patents related to the BCMA TAC described in this manuscript and licensed to Triumvira Immunologics.<br /> (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1477-2566
- Volume :
- 25
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cytotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 37306644
- Full Text :
- https://doi.org/10.1016/j.jcyt.2023.05.004