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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

Ganglioside GM2 expression in clinical malignant pleural mesothelioma specimens. Frozen sections obtained from 26 mesothelioma patients were incubated in DAPI at room temperature for 20 min. After washing, the sections were incubated in 5% FBS–PBS for 10 min for blocking and subsequently incubated in 30 μg/mL BIW-8962 or anti-dinitrophenol antibodies conjugated with Alexa Fluor488 at 4°C for 6 h. Representative images are shown. Samples of patients #12 (a), 19 (b), 20 (c), and 23 (d) are shown.
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fig04: Ganglioside GM2 expression in clinical malignant pleural mesothelioma specimens. Frozen sections obtained from 26 mesothelioma patients were incubated in DAPI at room temperature for 20 min. After washing, the sections were incubated in 5% FBS–PBS for 10 min for blocking and subsequently incubated in 30 μg/mL BIW-8962 or anti-dinitrophenol antibodies conjugated with Alexa Fluor488 at 4°C for 6 h. Representative images are shown. Samples of patients #12 (a), 19 (b), 20 (c), and 23 (d) are shown.

Mentions: In order to determine GM2 expression in clinical MPM specimens, immunofluorescent staining of frozen MPM tissue samples obtained from 26 patients was carried out. The GM2 expression was subsequently confirmed in 58% of the donors, although the intensity and frequency of staining varied greatly from donor to donor (Fig.4, Table2). In contrast, we found no correlation between GM2 expression pattern and MPM tissue type or stage. GM2 positivity was detected in four of eight biphasic type samples (50%), three of five desmoplastic type samples (60%), and one of two epithelial type samples (50%). Similarly, GM2-positive cells were detected in two of three stage I tumors (67%), three of four stage II tumors (75%), five of seven stage III tumors (71%), and two of five stage IV tumors (40%).


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)

Ganglioside GM2 expression in clinical malignant pleural mesothelioma specimens. Frozen sections obtained from 26 mesothelioma patients were incubated in DAPI at room temperature for 20 min. After washing, the sections were incubated in 5% FBS–PBS for 10 min for blocking and subsequently incubated in 30 μg/mL BIW-8962 or anti-dinitrophenol antibodies conjugated with Alexa Fluor488 at 4°C for 6 h. Representative images are shown. Samples of patients #12 (a), 19 (b), 20 (c), and 23 (d) are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig04: Ganglioside GM2 expression in clinical malignant pleural mesothelioma specimens. Frozen sections obtained from 26 mesothelioma patients were incubated in DAPI at room temperature for 20 min. After washing, the sections were incubated in 5% FBS–PBS for 10 min for blocking and subsequently incubated in 30 μg/mL BIW-8962 or anti-dinitrophenol antibodies conjugated with Alexa Fluor488 at 4°C for 6 h. Representative images are shown. Samples of patients #12 (a), 19 (b), 20 (c), and 23 (d) are shown.
Mentions: In order to determine GM2 expression in clinical MPM specimens, immunofluorescent staining of frozen MPM tissue samples obtained from 26 patients was carried out. The GM2 expression was subsequently confirmed in 58% of the donors, although the intensity and frequency of staining varied greatly from donor to donor (Fig.4, Table2). In contrast, we found no correlation between GM2 expression pattern and MPM tissue type or stage. GM2 positivity was detected in four of eight biphasic type samples (50%), three of five desmoplastic type samples (60%), and one of two epithelial type samples (50%). Similarly, GM2-positive cells were detected in two of three stage I tumors (67%), three of four stage II tumors (75%), five of seven stage III tumors (71%), and two of five stage IV tumors (40%).

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