Therapeutic activity of glycoengineered anti-GM2 antibodies against malignant pleural mesothelioma.
Bottom Line: BIW-8962 showed a significant antibody-dependent cellular cytotoxicity activity against the GM2-expressing MPM cell line MSTO-211H, the effect of which depended on the antibody concentration and effector/target ratio.Additionally, the GM2 expression was confirmed in the MPM clinical specimens.These data suggest that anti-GM2 antibodies may become a therapeutic option for MPM patients.
Affiliation: Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.Show MeSH
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Mentions: First, we carried out a flow cytometric analysis to determine the GM2 expression levels in the MPM cell lines. In this assay, 11 histologically different MPM cell lines were used, as follows: ACC-MESO-1, Y-MESO-12, NCI-H290, NCI-H513, NCI-H226, and NCI-H2452 as epithelioid type cells; NCI-H28 and NCI-H2052 as sarcomatoid type cells; and Y-meso-8A, Y-meso-14, and MSTO-211H as biphasic type cells. Membrane-bound GM2 antigens were detected using the anti-GM2 antibody BIW-8962. The GM2 expression levels in these cell lines were categorized into three groups based on the relative fluorescence intensity: high (>10) in four cell lines (36%); low (2–10) in four cell lines (36%); and negative (<2) in three cell lines (28%) (Fig.1). We found no cell type-dependent high expression of GM2, and no GM2 expression was detected in the sarcomatoid MPM cell lines.
Affiliation: Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.