Anti‐ BCMA CAR ‐ NK Cells Reveal Enhanced Cytolytic and Secretory Responses Against Myeloma Cells

Multiple myeloma (MM) is a hematologic malignancy characterized by uncontrolled malignant plasma cell proliferation. B‐cell maturation antigen (BCMA) is an attractive therapeutic target due to its high expression on malignant plasma cells. In this study, BCMA‐directed CAR‐NK‐92 cells were generated via lentiviral transduction of a second‐generation CAR construct. CAR expression was confirmed by flow cytometry (81% efficiency). Engineered cells were functionally evaluated against BCMA‐positive (U266, RPMI‐8226) myeloma cell lines, as well as BCMA‐negative control cells (K562, Jurkat). CAR‐NK‐92 cells demonstrated significantly enhanced cytotoxic activity against BCMA‐positive targets compared with parental NK‐92 cells (e.g., 87% vs. 54% cytotoxicity at 1:1, p < 0.001). Enhanced antitumor activity was accompanied by increased CD107α surface expression and elevated secretion of perforin, granzyme B, TNF‐α, and IFN‐γ ( p < 0.05). No significant differences in cytotoxicity or cytokine secretion were observed against BCMA‐negative control cells ( p > 0.05), supporting antigen‐specific activity. Importantly, CAR‐NK‐92 cells also exhibited potent cytotoxicity and significantly elevated cytokine secretion against primary CD138+ myeloma cells isolated from patient bone marrow aspirates. These findings demonstrate that anti‐BCMA CAR‐NK‐92 cells exhibit potent and selective antimyeloma activity in vitro, supporting CAR‐NK‐92 cells as an off‐the‐shelf immunotherapeutic platform for multiple myeloma.