Abstract
B cell maturation antigen (BCMA) has emerged as a prominent immunotherapeutic target in multiple myeloma (MM) due to its restricted expression on MM cells, plasma cells and mature B cells, with minimal presence in other normal tissues. In this study, we demonstrate through RNA sequencing and flow cytometry analyses of acute myeloid leukemia (AML) cell lines and primary patient samples that BCMA is also a relevant AML-associated antigen. Its robust surface expression on AML cells positions it as a promising candidate for targeted immunotherapy. Functionally, our findings indicate that BCMA in AML operates similarly to its role in MM - engaging the NF-kB pathway upon ligand binding, thereby activating gene expression programs that support leukemia cell survival and proliferation. We assessed several BCMA-targeted immunotherapeutic strategies, including bispecific T-cell engagers (TCE) and chimeric antigen receptor (CAR) transduced T-cells, NK-cells, and macrophages. We found that TCE treatment and BCMA CAR engineering markedly improved effector cell mediated cytotoxicity against AML cells, underscoring BCMA's potential as a viable therapeutic target in AML. Furthermore, BCMA- directed TCE therapy significantly augmented the anti-leukemic activity of adoptively transferred CD8(+) T-cells in a human AML xenograft model. Taken together, these findings support BCMA as a novel immunotherapeutic target in AML. Leveraging existing BCMA-directed treatments developed for MM could enable rapid clinical translation and broaden immunotherapy options for patients with AML.