Fig. 1.

Advantages of chimeric antigen receptor (CAR)-invariant NKTs (iNKTs). CAR-iNKT cells can recognize tumor cells through both their standard iNKT T-cell receptor (TCR) and the specific anti-tumor antigen CAR, leading to targeted cytotoxicity. The intracellular portion of the CAR consists of the CD3ζ domain for TCR signaling. The CAR can also be modified to include a co-stimulatory endodomain and a cytokine transgene to increase production of pro-inflammatory cytokines and enhance overall antitumor efficacy. CAR-iNKT cells hold great promise for immunotherapy as they overcome various obstacles that hinder the efficacy of other commonly used immunotherapies. CAR-iNKT cells can persist in vitro and in vivo to minimize tumor recurrence. Unlike traditional CAR-T cells composed of classic CD4 and CD8 T cells, CAR-iNKT cells do not induce an allogenic response against healthy cells and therefore prevent the induction of graft-versus-host disease (GVHD). CAR-iNKT cells can also infiltrate tumor sites and localize to tumor sites, maximizing their antitumor potential