Treatment of Hematologic Malignancies With Genetically Modified T Cells

The past decade has witnessed rapid progress in the field of T-cell therapies for hematologic malignancies, highlighted by the first US Food and Drug Administration (FDA) approved CD19-directed chimeric antigen-receptor (CAR)-T cell therapy in 2017, multiple subsequent FDA-approvals across several disease states, and currently with hundreds of ongoing clinical trials. This chapter will review the principles underlying adoptive cellular therapy with T lymphocytes, with a primary focus on genetically modified T cells. The chapter covers both artificially modified αβT-cell receptors and CARs, pivotal studies evaluating CAR-T-cell therapies, potential advantages of different T-cell subsets, strategies to optimize T-cell trafficking and overcome tumor immune evasion, and potential methods to improve the safety of T-cell therapy by including safety-switch genes and improving tumor cell specificity.