Using agonists for iNKT cells in cancer therapy. (February 2021)

• Record Type: Journal Article
• Authors: Painter, Gavin F.; Burn, Olivia K.; Hermans, Ian F.
• Is Part Of: Molecular immunology. Volume 130(2021)
• Page Start: 1
• Page End: 6
• Publication Date: 2021-02
• Subjects: iNKT cell -- iNKT cell agonists -- Immunotherapy; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2020.12.010
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: CAR iNKT cells show promise in a neuroblastoma clinical trial. CD1d-ligand covalent conjugates overcome NKT cell anergy. Liposomal formulations containing iNKT agonist compounds display potent vaccine adjuvant activity. Conjugation of peptide or carbohydrate antigens to iNKT agonist compounds increases the anti-tumour immune response. Abstract: The capacity of α-galactosylceramide (α-GalCer) to act as an anti-cancer agent in mice through the specific stimulation of type I NKT (iNKT) cells has prompted extensive investigation to translate this finding to the clinic. However, low frequencies of iNKT cells in cancer patients and their hypo-responsiveness to repeated stimulation have been seen as barriers to its efficacy. Currently the most promising clinical application of α-GalCer, or its derivatives, is as stimuli for ex vivo expansion of iNKT cells for adoptive therapy, although some encouraging clinical results have recently been reported using α-GalCer pulsed onto large numbers of antigen presenting cells (APCs). In on-going preclinical studies, attempts to improve efficacy of injected iNKT cell agonists have focussed on optimising presentation in vivo, through encapsulation in particulate vectors, making structural changes that help binding to the presenting molecule CD1d, or injecting agonists covalently attached to recombinant CD1d. Variations on these same approaches are being used to enhance the APC-licencing function of iNKT cells in vivo to induce adaptive immune responses to associated tumour antigens. Looking ahead, a unique capacity of in vivo -activated iNKT cells to facilitate formation of resident memory CD8 + T cells is a new observation that could find a role in cancer therapy.