Cellular Therapy with Engineered T Cells, Efficacy, and Side Effects: Gene Editing/Gene Therapy

The cellular basis of cancer immune surveillance, already hypothesized in ancient times, was only proven with the advent of HCT. Indeed, the discovery of the nature of GVHD and its antileukemic effects (Weiden et al. 1979) was followed by the first successful attempts of adoptive immunotherapy using donor leukocytes (Kolb et al. 1990). To address the significant GVHD risk associated with allogeneic T cells, several approaches of T-cell manipulation were developed and tested (Table 60.1). Some of these strategies rely on the genetic manipulation of T cells. First, suicide gene therapy approaches were established to promote GVL and immune reconstitution while controlling GVHD. More recently, strategies based on the genetic transfer of tumor-specific T-cell receptors (TCRs) or chimeric antigen receptors (CARs) were developed to improve antitumor efficiency of T cells. This chapter provides an overview of this vastly evolving area.