Delivery strategies for ex vivo and in vivo T-cell reprogramming

Abstract In recent years, the immune system has increasingly been recognized as a critical component to understanding cancer progression and cellular microenvironments. This has led to massive growth in the field of cancer immunotherapy, in which the patient's natural defense mechanisms are harnessed and enhanced to fight cancer. In this field, T-cell engineering has been the most widely studied and developed approach, with checkpoint inhibitors like anti-PD-1 antibody recently showing impressive clinical success for solid tumors and ex vivo engineering of chimeric antigen receptor T-cells making a significant impact on liquid tumors. There has been continued basic and translational research interest in developing engineering technologies for delivery of therapeutic agents to induce T-cell reprogramming both ex vivo and in vivo for cancer immunotherapy. In this chapter, delivery technologies that provide surface stimulation to T-cells (outside-in) as well as technologies that deliver intracellular mediators to T-cells (inside-out) for reprogramming to enhance anti-cancer activity are discussed.