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Start Over Descriptor "Ganglioside GM2" Journal cancer science
2 results on '"Ganglioside GM2"'

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

Author

Li, Qi, Wang, Wei, Machino, Yusuke, Yamada, Tadaaki, Kita, Kenji, Oshima, Masanobu, Sekido, Yoshitaka, Tsuchiya, Mami, Suzuki, Yui, Nan‐ya, Ken‐ichiro, Iida, Shigeru, Nakamura, Kazuyasu, Iwakiri, Shotaro, Itoi, Kazumi, and Yano, Seiji

Abstract

Malignant pleural mesothelioma ( MPM) is a rare and highly aggressive neoplasm that arises from the pleural, pericardial, or peritoneal lining. Although surgery, chemotherapy, radiotherapy, and combinations of these therapies are used to treat MPM, the median survival of such patients is dismal. Therefore, there is a compelling need to develop novel therapeutics with different modes of action. Ganglioside GM2 is a glycolipid that has been shown to be overexpressed in various types of cancer. However, there are no published reports regarding the use of GM2 as a potential therapeutic target in cases of MPM. In this study, we evaluated the efficacy of the anti- GM2 antibody BIW-8962 as an anti- MPM therapeutic using in vitro and in vivo assays. Consequently, the GM2 expression in the MPM cell lines was confirmed using flow cytometry. In addition, eight of 11 cell lines were GM2-positive (73%), although the GM2 expression was variable. 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. In an in vivo orthotropic mouse model using MSTO-211H cells, BIW-8962 significantly decreased the incidence and size of tumors. Additionally, the GM2 expression was confirmed in the MPM clinical specimens. Fifty-eight percent of the MPM tumors were positive for GM2, with individual variation in the intensity and frequency of staining. These data suggest that anti- GM2 antibodies may become a therapeutic option for MPM patients. [ABSTRACT FROM AUTHOR]

Published
2015
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2. Therapeutic activity of glycoengineered anti-GM2 antibodies against malignant pleural mesothelioma

Author

Seiji Yano, Shotaro Iwakiri, Shigeru Iida, Ken-ichiro Nan-ya, Wei Wang, Masanobu Oshima, Yusuke Machino, Yui Suzuki, Kenji Kita, Kazumi Itoi, Tadaaki Yamada, Kazuyasu Nakamura, Qi Li, Mami Tsuchiya, and Yoshitaka Sekido

Subjects
Male, Mesothelioma, Cancer Research, Pathology, medicine.medical_specialty, endocrine system, Lung Neoplasms, Pleural Neoplasms, medicine.medical_treatment, Antineoplastic Agents, G(M2) Ganglioside, Mice, SCID, Therapeutics, Antibodies, Monoclonal, Humanized, Protein Engineering, Antibodies, Flow cytometry, Antibody-dependent cell cytotoxicity, In vivo, Cell Line, Tumor, medicine, Animals, Humans, Neoplasm, Pleural Neoplasm, Aged, Aged, 80 and over, Chemotherapy, medicine.diagnostic_test, Ganglioside GM2, business.industry, Mesothelioma, Malignant, Cancer, Original Articles, General Medicine, Middle Aged, medicine.disease, Xenograft Model Antitumor Assays, Radiation therapy, carbohydrates (lipids), Oncology, Female, lipids (amino acids, peptides, and proteins), business
Abstract

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive neoplasm that arises from the pleural, pericardial, or peritoneal lining. Although surgery, chemotherapy, radiotherapy, and combinations of these therapies are used to treat MPM, the median survival of such patients is dismal. Therefore, there is a compelling need to develop novel therapeutics with different modes of action. Ganglioside GM2 is a glycolipid that has been shown to be overexpressed in various types of cancer. However, there are no published reports regarding the use of GM2 as a potential therapeutic target in cases of MPM. In this study, we evaluated the efficacy of the anti-GM2 antibody BIW-8962 as an anti-MPM therapeutic using in vitro and in vivo assays. Consequently, the GM2 expression in the MPM cell lines was confirmed using flow cytometry. In addition, eight of 11 cell lines were GM2-positive (73%), although the GM2 expression was variable. 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. In an in vivo orthotropic mouse model using MSTO-211H cells, BIW-8962 significantly decreased the incidence and size of tumors. Additionally, the GM2 expression was confirmed in the MPM clinical specimens. Fifty-eight percent of the MPM tumors were positive for GM2, with individual variation in the intensity and frequency of staining. These data suggest that anti-GM2 antibodies may become a therapeutic option for MPM patients. In this study, the anti-GM2 antibody BIW-8962 first showed a significant ADCC activity against malignant pleural mesothelioma (MPM) cell line and therapeutic activity in an in vivo orthotropic mouse model using the cell line. 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. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Published
2015

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