Immunobiology of chimeric antigen receptor T cells and novel designs

Advances in the development of immunotherapies have offered exciting new options for the treatment of malignant diseases that are refractory to conventional cytotoxic chemotherapies. The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has demonstrated dramatic results in clinical trials and highlights the promise of novel immune-based approaches to the treatment of cancer. As experience with CAR T cells has expanded with longer follow-up and to a broader range of diseases, new obstacles have been identified which limit the potential lifelong benefits of CAR T cell therapy. These obstacles highlight not only the gaps in knowledge of the optimal clinical application of this "living drug", but also gaps in our understanding of the fundamental biology of CAR T cells themselves. In this review, we discuss the obstacles facing CAR T cell therapy, how these relate to our current understanding of CAR T cell biology and approaches to enhance the clinical efficacy of this therapy.