CAR cellular therapies for acute myeloid leukemia: current landscape and future directions

Chimeric antigen T cell (CAR-T) therapy has revolutionized the treatment of B-cell malignancies, but has not seen this success replicated in acute myeloid leukemia (AML). Many antigens present on AML cells are shared with healthy hematopoietic progenitors, posing a risk of prohibitive toxicity with CAR-T therapy. Furthermore, clonal evolution of AML, antigen escape and effects of tumor microenvironment (TME) may hinder the efficacy of treatment. A number of innovative approaches to overcome these barriers have been attempted in recent years, including combinatorial and neoantigen targeting, logic-gated CARs, CAR-T armoring to overcome the effects of TME and CAR-T consolidation of engineered antigen-negative stem cell transplants. Despite this, no CAR-T treatments are currently licensed for AML. While some early trial data seems promising, it remains to be seen whether CAR-T therapy is a viable strategy for treatment of AML.