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Therapeutic activity of glycoengineered anti-GM2 antibodies against malignant pleural mesothelioma.

Li Q, Wang W, Machino Y, Yamada T, Kita K, Oshima M, Sekido Y, Tsuchiya M, Suzuki Y, Nan-Ya K, Iida S, Nakamura K, Iwakiri S, Itoi K, Yano S - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.

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Related in: MedlinePlus

Expression levels of ganglioside GM2 were evaluated in malignant pleural mesothelioma cell lines. Cells were detached and incubated with BIW-8962 or anti-dinitrophenol (DNP) antibodies on ice for 30 min. Bound Abs were detected with FITC-conjugated goat anti-human IgG Abs. The fluorescence intensity of the stained cells was measured using flow cytometry, and the mean fluorescence intensity was calculated. The open red histograms represent BIW-8962-stained samples and the filled blue histograms represent anti-DNP antibody-stained samples. The relative fluorescent intensity (RFI) versus anti-DNP is indicated.
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fig01: Expression levels of ganglioside GM2 were evaluated in malignant pleural mesothelioma cell lines. Cells were detached and incubated with BIW-8962 or anti-dinitrophenol (DNP) antibodies on ice for 30 min. Bound Abs were detected with FITC-conjugated goat anti-human IgG Abs. The fluorescence intensity of the stained cells was measured using flow cytometry, and the mean fluorescence intensity was calculated. The open red histograms represent BIW-8962-stained samples and the filled blue histograms represent anti-DNP antibody-stained samples. The relative fluorescent intensity (RFI) versus anti-DNP is indicated.

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.


Therapeutic activity of glycoengineered anti-GM2 antibodies against malignant pleural mesothelioma.

Li Q, Wang W, Machino Y, Yamada T, Kita K, Oshima M, Sekido Y, Tsuchiya M, Suzuki Y, Nan-Ya K, Iida S, Nakamura K, Iwakiri S, Itoi K, Yano S - Cancer Sci. (2014)

Expression levels of ganglioside GM2 were evaluated in malignant pleural mesothelioma cell lines. Cells were detached and incubated with BIW-8962 or anti-dinitrophenol (DNP) antibodies on ice for 30 min. Bound Abs were detected with FITC-conjugated goat anti-human IgG Abs. The fluorescence intensity of the stained cells was measured using flow cytometry, and the mean fluorescence intensity was calculated. The open red histograms represent BIW-8962-stained samples and the filled blue histograms represent anti-DNP antibody-stained samples. The relative fluorescent intensity (RFI) versus anti-DNP is indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317781&req=5

fig01: Expression levels of ganglioside GM2 were evaluated in malignant pleural mesothelioma cell lines. Cells were detached and incubated with BIW-8962 or anti-dinitrophenol (DNP) antibodies on ice for 30 min. Bound Abs were detected with FITC-conjugated goat anti-human IgG Abs. The fluorescence intensity of the stained cells was measured using flow cytometry, and the mean fluorescence intensity was calculated. The open red histograms represent BIW-8962-stained samples and the filled blue histograms represent anti-DNP antibody-stained samples. The relative fluorescent intensity (RFI) versus anti-DNP is indicated.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.

Show MeSH
Related in: MedlinePlus