T Cell Receptors-Gene-Modified T Cells for Cancer: Methods, Data, and Challenges

Abstract

Cellular immunotherapy is currently one of the most exciting and promising new cancer treatments to reach the clinic. Expanded knowledge of T cell biology and new developments in synthetic biology have led to an ability to engineer T cells to express antibody-like recognition molecules linked to T cell-activating domains (chimeric antigen receptors, CARs) and tumor-specific T cell receptors (TCRs) which redirect patient-derived T cells toward their cancers. In this chapter, we will review the biology of T cell receptors, describe the rationale for generating affinity-enhanced TCRs with particular emphasis on the development of the affinity-enhanced NY-ESO-1-specific TCR. We also review clinical trials using TCR-engineered autologous T cells and highlight some important toxicities that have been observed in these studies. Finally, we provide an overview of some of the opportunities and challenges for wider application of this technology.