Engineering T Cells to Target Tumor Cells

The immune system can exert dual roles in cancer biology. Cellular elements serve both as an effector function to eradicate tumor cells and as a promoter to support tumor growth. The microenvironment of an established tumor is usually immune suppressive, protecting tumor cells from recognition and elimination by effector cells. Genetic engineering can be used to modify T cells ex vivo to improve their functionality in favor of tumor killing. Adoptive cell therapy with genetically modified T cells aims to (1) redirect specificity to tumor cell antigens, (2) increase the number and persistence of antigen-specific T cells, (3) improve T cell effector functions, (4) overcome suppression of T cells by disrupting inhibitory molecules, and (5) guide T cells to the tumor site through the interaction between chemokines and their receptors. T cells can be also equipped with suicide genes for their conditional elimination if they induce an unintended immune response or transform to a malignant phenotype. In this chapter, we describe the current status of adoptive therapy for cancer with genetically engineered T cells.