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NKT and iNKT Cells

المؤلف:  Armin Ghobadi & John F. DiPersio

المصدر:  Gene and Cellular Immunotherapy for Cancer

الجزء والصفحة:  p62

2026-08-19

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 While NK cells can be easily distinguished from T-cells by the lack of a TCR, NKT cells have markers typical of NK cells, such as NK1.1, but also contain an αβ ΤCR, and fall within the T-cell lineage. Unlike the αβ ΤCR of conventional T-cells that recognize peptides displayed on MHC-I, the αβ ΤCR of NKT cells recognizes glycolipid antigens presented on CD1d. Type I NKT cells (invariant or iNKT) possess a semi-invariant Vα14-Jα18 TCR in mice, and Vα24-Jα18 in humans paired with a limited repertoire of Vβ-chains making them an attractive choice for allogeneic cells. Type II NKT cells utilize a more diverse TCR repertoire, although still almost all exclusively recognize glycolipids presented on CD1d due to their positive selection process in the thymus. Rather than inducing GVHD like their conventional T-cell counterpart in allogeneic infusions, NKT cells are associated with protection from GVHD, further increasing their appeal for allogeneic therapy. CD1d is expressed on some tumors, allowing for additional killing through this receptor. They also are reported to express CD40L, an activating molecule for macro phages and dendritic cells, which may help to favorably remodel the tumor microenvironment. Since NKT cells are a type of T-cell, they expand and persist much more readily than NK cells. However, engineering sufficient numbers for therapy is still a challenge since they naturally make up <1% of peripheral T-cells. Ongoing clinical trials testing CAR NKT cells for GD2 (NCT03294954) and CD19 (NCT03774654) expressing malignancies are expected to offer more insight into their safety and feasibility in humans.