Immunotherapy targeting mesothelin in acute myeloid leukemia

Abstract

Mesothelin (MSLN) is an emerging target that exists in soluble and membrane-associated forms. It is usually used for the diagnosis and treatment of MSLN-positive solid tumors. Interestingly, recent studies have shown that MSLN is highly expressed in 36% of acute myeloid leukemia (AML) patients and barely expressed in normal hematopoietic cells, which makes MSLN a promising target for the treatment of AML. It has been shown that MSLN is detectable as a diagnostic marker in its soluble form. Although the mechanism of action is unclear, MSLN remains a promising target for immunotherapy. Most MSLN research has been conducted in solid tumors, and less research has been conducted in hematopoietic tumors. Increasing research on MSLN is underway in AML, a hematopoietic neoplasm. For example, MSLN is related to extramedullary disease, minimal residual disease, and relapse in AML patients. Decreasing the expression of MSLN reduces the severity of the disease course. This information suggests that MSLN may be an ideal target for the treatment of many AML-related diseases to improve the prognosis and survival rate. At present, there are a few immunotherapies targeting MSLN in AML in preclinical and clinical trials, such as antibody-drug conjugates, bispecific T-cell engagers, and chimeric antigen receptor-T cells, which opens new room for the treatment of MSLN-related AML.

Keywords: acute myeloid leukemia; immunotherapy; mesothelin.