Week 11: Investigating the Potential of iNKT Cells

Hello! This week I’ll be discussing Invariant Natural Killer T cells and how they relate to building “Off-the-Shelf” CAR T-cells.

Invariant Natural Killer Cells

Invariant Natural Killer T cells are natural killer cells that possess a semi-invariant T cell protein receptor, a receptor that is genetically identical to every human. iNKTs make up less than 1% of the total lymphocyte population in humans; however, they play an important role in immune suppression and anti-tumor activity.

CAR-iNKT Cells

iNKT cells may be a wonderful source for allogeneic CAR T-cells as they do not induce Graft v. Host disease. Why? T cell receptor (TCR) proteins which are on the surface of T cells vary with each individual. When foreign cells with TCRs are administered to a patient, the foreign TCRs will attack the patient’s cells. iNKT cells have TCRs that are accepted by the immune cells in the patient As a result, CAR-iNKTs do not require TCR deletion which may be responsible for altering CAR T-cell persistence. (Stenger et al., 2020)

Current clinical trials are investigating allogeneic CAR-iNKT cells in patients with B-cell cancers. The CAR T-cell therapy is accompanied by a lymphodepletion treatment which is a chemotherapy that kills immune cells that could reject the allogeneic cells. While CAR-iNKT may not last in a patient in the long-term, they cause long-lasting host killer T cell anti-tumor activity (Simonetta et al., 2021) Future research must be conducted to determine the extent of HLA matching and chemotherapy needed for CAR-iNKT treatments.

Conclusion

While iPSCs, NK cells, or donor-derived T cells may be the optimal cell type for “Off-the-Shelf” CAR T-cells, it’s important to examine other cells such as iNKTs. iNKTs hold immense promise because they may possess the best characteristics of T cells and NK cells. They may also be much safer as compared to CAR T-cells as they will not induce Graft vs. Host disease.

Tune in next week as I continue my quest to “Off-the-Shelf” CAR T-cells.

Sidharth