Fifteen years of gene therapy based on chimeric antigen receptors: Are we nearly there yet?

T-body or chimeric antigen receptor (CAR) technology, which combines the specificity of an antibody with the homing, tissue penetration, and target cell destruction of T cells, was first described in 1993. After many years of unmet promise, significant improvements in gene transfer, including the development of efficient retroviral vectors for transduction of human T cells, and better understanding of immunological pathways and immune cell interactions, are allowing this technology to reach a critical phase of evaluation, in which we will learn whether the approach can truly meet expectations. In this review we summarize the concept of CAR-based immunotherapy, describe the steps accomplished, and outline the future progress we need to make if this approach is truly to improve cancer immunotherapy.