Chimeric antigen receptor T-cell therapy in acute myeloid leukaemia: Novel therapeutic approaches to longstanding challenges

Abstract

Despite the approval of several novel targeted therapies since 2017, acute myeloid leukaemia (AML) remains a devastating disease with high rates of relapse and a dismal prognosis. The heterogeneity of AML and poor tolerance of chemotherapeutic agents by the elderly necessitates that further treatment options are required. Chimeric antigen receptor (CAR) T-cell therapy is a form of adoptive cell-transfer based immunotherapy that leverages the use of genetically modified T cells to direct antigen specific cytotoxicity. Anti-CD19 and anti-B-cell maturation antigen (BCMA) CAR T-cell therapy have demonstrated remarkable therapeutic efficacy in B cell lymphomas and leukaemias and in multiple myeloma respectively. However, the clinical utility of CAR T-cell therapy has not yet extended to other malignancies. In the case of AML, this has been particularly hindered by a lack of suitable targeting antigens that specifically eliminate leukaemic cells whilst sparing normal healthy haematopoietic stem/progenitor cells (HSPCs). In this review, we highlight the pertinent challenges and barriers to effective CAR T-cell therapy in AML, as well as recent strategies to overcome them.