Figure 3.

Functional advantages of chimeric antigen receptor (CAR)-invariant natural killer T (iNKT) cells over conventional CAR-T cells. The structure of a third-generation anti-CD19 CAR-iNKT cell is depicted interacting with both a target CD19+ tumor cells and a healthy bystander cell. Third generation CARs have three endodomains that can be modified to tune the response of the iNKT cell when activated. Similar to conventional iNKT cells, CAR-iNKT cells would be able to directly kill tumor cells using Fas:FasL interactions and secretion of perforin/granzyme. CAR-iNKT cells also secrete stimulatory cytokines, such as IFN-γ, that can license dendritic cells as well as indirectly activate cytotoxic T lymphocytes and natural killer cells to kill tumor cells (not depicted). The CAR-iNKT cells is juxtaposed to a similar CAR-T cell to highlight a few key differences between CARs in iNKT cells and CARs in conventional T cells (differences are underlined). Skull and crossbones indicate cell killing.