Fig. 3.

Exploiting ICOS and OX40 in CAR Th17/Tc17 cells redirected to recognize and kill tumors. Gene transfer is used to redirect lymphocytes to express chimeric antigen receptors that target tumor antigens in an MHC-independent manner. CARs are fusion proteins composed of an extracellular portion derived from an antibody (ScFv), a linker that dimerizes with intracellular signaling domains derived from T cell signaling proteins. CAR constructs used in the clinic contain CD3ζ as well as a co-stimulatory endodomains (e.g., CD28 or 4-1BB). CARs to generate Th17 cells consist of an ICOS co-stimulatory endodomains linked to CD3ζ. An OX40 co-stimulatory domain could possibly be added to enhance antitumor immunity, as OX40/OX40 ligand signaling favors effector T cells over Treg cells