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Constitutive expression of interleukin-27 diminishes proinflammatory cytokine production without impairing effector

Arya Afsahi1, Rebecca Burchett1, Christopher L Baker1

  • 1Centre for Discovery in Cancer Research, McMaster University, Hamilton, Ontario, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Cytotherapy
|June 12, 2023
PubMed

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.

Keywords:
IL-27TRUCKcancer immunotherapyengineered T cellmultiple myeloma

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