Chapter 30 - Adoptive Cellular Therapy With Synthetic T Cells as an “Instant Vaccine” for Cancer and Immunity

Abstract

The field of adoptive cell transfer (ACT) is currently comprised of chimeric antigen receptor (CAR)- and T-cell receptor (TCR)-engineered T cells and has emerged from principles of basic immunology to paradigm-shifting clinical immunotherapy for cancer. ACT of T cells engineered to express artificial receptors that target cells of choice is an exciting new approach for cancer, and it holds equal promise for chronic infection and autoimmunity. Here, the notion that “instant vaccines” can be created and delivered using principles of synthetic biology, advances in immunology, and genetic engineering to generate human T cells that display desired specificities and enhanced functionalities is reviewed. Clinical trials in patients with advanced B-cell leukemias and lymphomas treated with CD19-specific CAR T cells have induced durable remissions in adults and children. Advances in cell engineering and culture approaches to enable efficient gene transfer and ex vivo cell expansion have facilitated broader evaluation of this technology, moving adoptive transfer from a “boutique” application to the cusp of a mainstream technology. The prospects for the widespread availability of engineered T cells have changed dramatically, given the recent entry of the pharmaceutical industry to this field. In this chapter, the blurring of distinction between vaccinology and adoptive transfer, and some of the challenges and opportunities that are faced by the emerging field of ACT will be discussed.