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.