Exploiting CD1-restricted T cells for clinical benefit. (April 2021)

• Record Type: Journal Article
• Authors: Exley, Mark A.; Dellabona, Paolo; Casorati, Giulia
• Is Part Of: Molecular immunology. Volume 132(2021)
• Page Start: 126
• Page End: 131
• Publication Date: 2021-04
• Subjects: CD1 -- CD1a -- CD1b -- CD1c -- CD1d -- iNKT cells; 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.2020.12.015
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: CD1-restricted T cells including Invariant Natural Killer cells (iNKT) are innate lymphocytes with potent cytotoxic and cytokine effector functions. Highly-specific methods have been developed for therapeutic targeting of iNKT cells in cancers, inflammatory, infectious and autoimmune diseases. Uniform safety, evidence of immunologic activity and increasingly clinical efficacy have been seen. Approaches to targeting iNKT cells in clinical development include natural glycolipid ligands, chemical analogues thereof and monoclonal antibody-based targeting. Approaches to targeting iNKT cells in clinical development include natural glycolipid ligands, chemical analogues thereof and monoclonal antibody-based targeting. Abstract: CD1-restricted T cells were first described over 30 years ago along with the cloning of the CD1 family. Around the same time, invariant Natural Killer cells (iNKT) were identified based on invariant TCR-alpha chains with additional expression of natural killer (NK) cell markers. About 5 years later, iNKT were shown to react with CD1d. Since then, iNKT have been shown to be a major population of CD1d-restricted T cells in humans and many animals. Like NK cells, iNKT are innate lymphocytes with rapid and wide-ranging effector potential. These activities include cytotoxicity and an unusually broad and high-level cytokine production. The development of highly-specific methods of isolating, stimulating, expanding or depleting these relatively rare cells and controlling their potent activities has stimulated considerable interest in therapeutic targeting of iNKT cells. Potential applications include cancers, inflammatory, infectious and autoimmune among other diseases. To date, most trials have targeted various cancers, there are 2 published trials in viral hepatitis and one in sickle cell lung disease. Uniform safety, evidence of immunologic activity and increasingly clinical efficacy have been seen. Approaches to targeting iNKT cells in clinical development include highly specific natural glycolipid ligands presented by CD1d and chemical analogues thereof and monoclonal antibody-based targeting of iNKT cells. In the case of iNKT cell-based therapies, novel approaches include arming them with Chimeric Antigen Receptors (CARs) and recombinant TCRs (rTCR), gene editing and allogeneic use. Controlling the iTCR:CD1d molecular interaction and consequences is a unique and promising therapeutic technology.