iNKT: A new avenue for CAR-based cancer immunotherapy

Chimeric antigen receptor (CAR) T cell is a T lymphocyte-based immunotherapy, which achieves great successes in treating blood malignancies and provides new hope to cue advanced cancer patients. Invariant natural killer T (iNKT) cells are a kind of special T lymphocytes characterized by expressing invariant TCR of Vα24Vβ11 to recognize CD1d-presented glycolipid antigens, which bridge innate and adaptive immune responses. iNKT cells themselves show strong anti-tumor effect in tumor models via CD1d-mediated killing of CD1d-positive tumor cells and immunosuppressive TAMs and MDSCs, and are closely related to the prognosis of cancer patients. iNKT cells are not restricted to polymorphic human leukocyte antigen (HLA) and can prevent Graft versus Host Disease (GvHD), which makes it to be an ideal CAR vector for allogeneic therapy. Although CAR-iNKT was developed and verified by several different teams and attracts more and more attentions, many obstacles are still needed to be resolved before obtaining CAR-iNKT therapeutics. In this review, we summarized the current status of clinical application of iNKT cells and the latest achievements of CAR-iNKT cells, which provides new insight in CAR-iNKT development and usages.