B-cell maturation antigen (BCMA) was recently identified as a target of T-cell-directed therapy for acute myeloid leukemia (AML), based on the study reporting high BCMA abundance in AML cells using the flow cytometry anti-BCMA antibody clone 19F2 (BCMA-19F2). However, our independent investigation demonstrated limited BCMA levels in both AML patient samples and AML cell lines through the analysis of established transcriptome profiles. The low BCMA expression in AML cells was validated by flow cytometry using an alternative anti-BCMA antibody (clone REA315) and western blotting. Importantly, we unveiled that the BCMA-19F2 could bind non-specifically to AML cells via its non-antigen-binding fragment, as evidenced by the isotype control experiment and Fc receptor blocking assay. Furthermore, cytotoxicity assay confirmed that the leukemic cell lysis was minimal on the treatment of anti-BCMA CAR T cells. Our data suggest that BCMA expression is restricted in AML, and the BCMA-19F2 is unsuitable for BCMA detection in the context of AML samples. It underscores that the accurate assessment of tumor antigen is paramount for therapeutic target design.
Ran et al. (Sun,) studied this question.