Figure 2.

Novel Approaches to Improve CAR T Cell Anti-Tumor Efficacy. Armored CAR T cells have been designed to protect T cells from the immunosuppressive tumor microenvironment by expressing cytokines, as an independent gene within the CAR vector. Tandem CAR T cells have been designed to express two antigen-binding domains arranged in tandem with one intracellular signaling domain. Multi-CAR T Cells consist of one T-cell expressing two CAR structs with different antigen binding domains, with one CAR containing an intracellular and the other a co-stimulatory domain. The presence of both antigens is required to efficiently activate the T cell. Switchable CAR T cells expresses a CAR joined to a co-stimulatory signaling domain. The CD3-ζ intracellular signaling domain can heterodimerize with the CAR co-stimulatory domain only in the presence of a small molecule which acts as an ‘ON’ switch. Thus, both interaction with target antigen and the small molecule are required for activation of the CAR T-cell. This figure was created with images adapted from Servier Medical Art by Servier. Original images are licensed under a Creative Commons Attribution 3.0 Unported License.