Chimeric Antigen Receptor Therapy in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogeneous clonal disease of myeloid-stem and progenitor cells that results from mutations, deletions, and epigenetic alterations in genes associated with cell differentiation, proliferation, and renewal. Although chemotherapeutic options for the treatment of AML exist, T-cell–mediated allogeneic hematopoietic cell transplant remains the only potentially curative option. Significant advances have been made in the last decade in the field of adoptive T-cell therapy, particularly in lymphoid neoplasms, and intense investigation is underway in a variety of both solid and hematologic malignancies. Various surface and signaling targets for AML have been proposed, and multiple clinical trials are underway; however, this field remains in the early stages of clinical investigation, in the setting of significant on-target, off-tumor effects on the hematopoietic compartment and organ tissues lead to profound toxicity and remain a significant hurdle. This chapter will review the potential for chimeric antigen receptor T-cell therapy for AML, as well as the common obstacles to successful clinical application.