Le Q, Castro S, Tang T, et al. Therapeutic Targeting of Mesothelin with Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia. Clinical Cancer Research. 2021; (doi: 10.1158/1078-0432.CCR-21-1546).
Researchers say chimeric antigen receptor (CAR) T-cell therapy targeted at mesothelin (MSLN) is a promising treatment pathway for acute myeloid leukemia (AML). Although MSLN as an antigen is heavily expressed in AML, the same does not apply to normal hematopoietic stem and progenitor cells (HSPC). Employing xenograft models, investigators demonstrated that MSLN-directed CAR T cells aggressively eradicate MSLN-positive AML cells with no impact on usual HSPC function. They also determined that preventing MSLN shedding, which is promoted by the ADAM17 metalloprotease, can increase the efficacy of CAR T-cell functionality.