Application of Chimeric Antigen Receptor T Cells in the Treatment of Hematological Malignancies

Abstract

T cell immune protection plays a pivotal role in the treatment of patients with hematological malignancies. However, T cell exhaustion might lead to the possibility of immune escape of hematological malignancies. Adoptive cell therapy (ACT) with chimeric antigen receptor T (CAR-T) cells can restore the activity of exhausted T cell through reprogramming and is widely used in the treatment of relapsed/refractory (r/r) hematological malignancies. Of note, CD19, CD20, CD30, CD33, CD123, and CD269 as ideal targets have shown extraordinary potential for CAR-T cell therapy and other targets such as CD23 and SLAMF7 have brought promising future for clinical trials. However, CAR-T cells can also produce some adverse events after treatment of hematological malignancies, such as cytokine release syndrome (CRS), neurotoxicity, and on-target/off-tumor toxicity, which may cause systemic immune stress inflammation, destruction of the blood-brain barrier, and even normal tissue damage. In this review, we aim to summarize the composition of CAR-T cell and its application in the treatment of acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), Hodgkin’s lymphoma (HL), multiple myeloma (MM), and acute myeloid leukemia (AML). Moreover, we will review the disadvantages of CAR-T cell therapy and propose several comprehensive recommendations which might guide its development.