Chimeric Antigen Receptor Therapies

Chimeric antigen receptor (CAR) T cells directed against CD19 for B-cell malignancies represent the first form of gene-transfer therapy to gain FDA approval. CARs are synthetic receptors that reprogram T cells to target cell-surface antigens following the transfer of genes encoding engineered T-cell receptors. CAR T-cell therapy combines the specificity of an antibody with the cytotoxic and memory functions of T cells. Once infused, each CAR T cell can kill many tumor cells. This chapter discusses the principles of synthetic immunity, efficacy against various tumor types, role of apheresis in manufacturing the product, toxic effects, tumor antigen escape, other challenges, and potential future applications of CAR T-cell therapy. Although autologous CAR T-cell therapies have immense potential, the cost and complexity of autologous T-cell therapies remain problematic. Emerging techniques may provide an opportunity to generate off-the-shelf T cells that combine favorable attributes, including antigen specificity, lack of alloreactivity, histocompatibility, and enhanced functional properties.