Immunotherapy of Brain Cancers: The Past, the Present, and Future Directions

Figure 1

Chimeric Antigen Receptors (CAR) used for potential human therapies of brain cancers. The monoclonal antibody towards either her2/neu, EGFRvIII, ganglioside GD3, or IL13Rα2 is the initial source of the genetic material. The first domains of the heavy and light chains are ligated together with a short spacer region to create the single chain variable fragment (scFv), to preserve the recombinant proteins’ antigen binding region. Another spacer region is ligated from the scFV region to the transmembrane CD28 molecule, followed by the TCRζ chain. After the T cells are transfected with the adenoviral construct, these T cells are then allowed to interact with the tumors. Upon contact with the antigen on the tumor, the CAR is activated and the TCRζ chain is now activated which then stimulates antitumor mediator effector function, that is, cytolysin or cytokine release.