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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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Anti-GM2 antibody BIW-8962 exerted antibody-dependent cellular cytotoxicity activity against MSTO-211H malignant pleural mesothelioma cells. Human peripheral blood mononuclear cells were purified from healthy donors and used as effector cells. MSTO-211H cells (target cells) were incubated with effector cells (effector/target = 25/1, 50/1, and 100/1) and antibodies (BIW-8962 or anti-dinitrophenol antibodies) at 37°C for 4 h. The released lactate dehydrogenase activity was measured and the % cytotoxicity was calculated. The experiments were carried out in triplicate, and the values are expressed as the mean of the values for four donors ± SD. *P < 0.01, **P < 0.001 BIW-8962 treatment versus anti-dinitrophenol antibody treatment.
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fig02: Anti-GM2 antibody BIW-8962 exerted antibody-dependent cellular cytotoxicity activity against MSTO-211H malignant pleural mesothelioma cells. Human peripheral blood mononuclear cells were purified from healthy donors and used as effector cells. MSTO-211H cells (target cells) were incubated with effector cells (effector/target = 25/1, 50/1, and 100/1) and antibodies (BIW-8962 or anti-dinitrophenol antibodies) at 37°C for 4 h. The released lactate dehydrogenase activity was measured and the % cytotoxicity was calculated. The experiments were carried out in triplicate, and the values are expressed as the mean of the values for four donors ± SD. *P < 0.01, **P < 0.001 BIW-8962 treatment versus anti-dinitrophenol antibody treatment.

Mentions: The in vitro ADCC activity of BIW-8962 against the MPM cell line was determined using MNCs obtained from four healthy volunteers as effector cells and MSTO-211H, as target cells, which highly express GM2. Consequently, BIW-8962 showed significant ADCC activity at antibody concentrations of 1 and 10 μg/mL (Fig.2), the efficacy of which increased in correlation with the E/T ratio (25, 50, and 100). The potent ADCC activity of BIW-8962 was consistently observed in MNCs obtained from the four donors.


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)

Anti-GM2 antibody BIW-8962 exerted antibody-dependent cellular cytotoxicity activity against MSTO-211H malignant pleural mesothelioma cells. Human peripheral blood mononuclear cells were purified from healthy donors and used as effector cells. MSTO-211H cells (target cells) were incubated with effector cells (effector/target = 25/1, 50/1, and 100/1) and antibodies (BIW-8962 or anti-dinitrophenol antibodies) at 37°C for 4 h. The released lactate dehydrogenase activity was measured and the % cytotoxicity was calculated. The experiments were carried out in triplicate, and the values are expressed as the mean of the values for four donors ± SD. *P < 0.01, **P < 0.001 BIW-8962 treatment versus anti-dinitrophenol antibody treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Anti-GM2 antibody BIW-8962 exerted antibody-dependent cellular cytotoxicity activity against MSTO-211H malignant pleural mesothelioma cells. Human peripheral blood mononuclear cells were purified from healthy donors and used as effector cells. MSTO-211H cells (target cells) were incubated with effector cells (effector/target = 25/1, 50/1, and 100/1) and antibodies (BIW-8962 or anti-dinitrophenol antibodies) at 37°C for 4 h. The released lactate dehydrogenase activity was measured and the % cytotoxicity was calculated. The experiments were carried out in triplicate, and the values are expressed as the mean of the values for four donors ± SD. *P < 0.01, **P < 0.001 BIW-8962 treatment versus anti-dinitrophenol antibody treatment.
Mentions: The in vitro ADCC activity of BIW-8962 against the MPM cell line was determined using MNCs obtained from four healthy volunteers as effector cells and MSTO-211H, as target cells, which highly express GM2. Consequently, BIW-8962 showed significant ADCC activity at antibody concentrations of 1 and 10 μg/mL (Fig.2), the efficacy of which increased in correlation with the E/T ratio (25, 50, and 100). The potent ADCC activity of BIW-8962 was consistently observed in MNCs obtained from the four donors.

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