Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity

Yukinari Kato; Akiko Kunita; Masashi Fukayama; Shinji Abe; Yasuhiko Nishioka; Hiroaki Uchida; Hideaki Tahara; Shinji Yamada; Miyuki Yanaka; Takuro Nakamura; Noriko Saidoh; Kanae Yoshida; Yuki Fujii; Ryusuke Honma; Michiaki Takagi; Satoshi Ogasawara; Takeshi Murata; Mika K. Kaneko

doi:10.1089/mab.2016.0045

Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity

Yukinari Kato, Akiko Kunita, Masashi Fukayama, Shinji Abe, Yasuhiko Nishioka, Hiroaki Uchida, Hideaki Tahara, Shinji Yamada, Miyuki Yanaka, Takuro Nakamura, Noriko Saidoh, Kanae Yoshida, Yuki Fujii, Ryusuke Honma, Michiaki Takagi, Satoshi Ogasawara, Takeshi Murata, Mika K. Kaneko

MED - Medical Sciences

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

Abstract

The interaction between podoplanin (PDPN) and C-type lectin-like receptor 2 (CLEC-2) is involved in tumor malignancy. We have established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-21, one of the mouse antipodoplanin mAbs, is of the IgG_2a subclass, and its minimum epitope was determined to be Thr76-Arg79 of the human podoplanin. Importantly, sialic acid is linked to Thr76; therefore, LpMab-21 is an antiglycopeptide mAb (GpMab). In this study, we investigated whether LpMab-21 shows antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human podoplanin-expressing cancer cell lines in vitro and also studied its antitumor activities using a xenograft model. LpMab-21 showed high ADCC and CDC activities against not only podoplanin-expressing Chinese hamster ovary cells but also LN319 glioblastoma cells and PC-10 lung cancer cells, both of which endogenously express podoplanin. Furthermore, LpMab-21 decreased tumor growth in vivo, indicating that LpMab-21 could be useful for antibody therapy against human podoplanin-expressing cancers.

Original language	English
Pages (from-to)	20-24
Number of pages	5
Journal	Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
Volume	36
Issue number	1
DOIs	https://doi.org/10.1089/mab.2016.0045
Publication status	Published - 2017 Feb

Keywords

ADCC
Antitumor activity
CDC
Monoclonal antibody
Podoplanin

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1089/mab.2016.0045

Cite this

Kato, Y., Kunita, A., Fukayama, M., Abe, S., Nishioka, Y., Uchida, H., Tahara, H., Yamada, S., Yanaka, M., Nakamura, T., Saidoh, N., Yoshida, K., Fujii, Y., Honma, R., Takagi, M., Ogasawara, S., Murata, T., & Kaneko, M. K. (2017). Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity. Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 36(1), 20-24. https://doi.org/10.1089/mab.2016.0045

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title = "Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity",

abstract = "The interaction between podoplanin (PDPN) and C-type lectin-like receptor 2 (CLEC-2) is involved in tumor malignancy. We have established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-21, one of the mouse antipodoplanin mAbs, is of the IgG2a subclass, and its minimum epitope was determined to be Thr76-Arg79 of the human podoplanin. Importantly, sialic acid is linked to Thr76; therefore, LpMab-21 is an antiglycopeptide mAb (GpMab). In this study, we investigated whether LpMab-21 shows antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human podoplanin-expressing cancer cell lines in vitro and also studied its antitumor activities using a xenograft model. LpMab-21 showed high ADCC and CDC activities against not only podoplanin-expressing Chinese hamster ovary cells but also LN319 glioblastoma cells and PC-10 lung cancer cells, both of which endogenously express podoplanin. Furthermore, LpMab-21 decreased tumor growth in vivo, indicating that LpMab-21 could be useful for antibody therapy against human podoplanin-expressing cancers.",

keywords = "ADCC, Antitumor activity, CDC, Monoclonal antibody, Podoplanin",

author = "Yukinari Kato and Akiko Kunita and Masashi Fukayama and Shinji Abe and Yasuhiko Nishioka and Hiroaki Uchida and Hideaki Tahara and Shinji Yamada and Miyuki Yanaka and Takuro Nakamura and Noriko Saidoh and Kanae Yoshida and Yuki Fujii and Ryusuke Honma and Michiaki Takagi and Satoshi Ogasawara and Takeshi Murata and Kaneko, {Mika K.}",

year = "2017",

month = feb,

doi = "10.1089/mab.2016.0045",

language = "English",

volume = "36",

pages = "20--24",

journal = "Monoclonal Antibodies in Immunodiagnosis and Immunotherapy",

issn = "2167-9436",

publisher = "Mary Ann Liebert Inc.",

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Kato, Y, Kunita, A, Fukayama, M, Abe, S, Nishioka, Y, Uchida, H, Tahara, H, Yamada, S, Yanaka, M, Nakamura, T, Saidoh, N, Yoshida, K, Fujii, Y, Honma, R, Takagi, M, Ogasawara, S, Murata, T & Kaneko, MK 2017, 'Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity', Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, vol. 36, no. 1, pp. 20-24. https://doi.org/10.1089/mab.2016.0045

Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity. / Kato, Yukinari; Kunita, Akiko; Fukayama, Masashi et al.
In: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Vol. 36, No. 1, 02.2017, p. 20-24.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity

AU - Kato, Yukinari

AU - Kunita, Akiko

AU - Fukayama, Masashi

AU - Abe, Shinji

AU - Nishioka, Yasuhiko

AU - Uchida, Hiroaki

AU - Tahara, Hideaki

AU - Yamada, Shinji

AU - Yanaka, Miyuki

AU - Nakamura, Takuro

AU - Saidoh, Noriko

AU - Yoshida, Kanae

AU - Fujii, Yuki

AU - Honma, Ryusuke

AU - Takagi, Michiaki

AU - Ogasawara, Satoshi

AU - Murata, Takeshi

AU - Kaneko, Mika K.

PY - 2017/2

Y1 - 2017/2

N2 - The interaction between podoplanin (PDPN) and C-type lectin-like receptor 2 (CLEC-2) is involved in tumor malignancy. We have established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-21, one of the mouse antipodoplanin mAbs, is of the IgG2a subclass, and its minimum epitope was determined to be Thr76-Arg79 of the human podoplanin. Importantly, sialic acid is linked to Thr76; therefore, LpMab-21 is an antiglycopeptide mAb (GpMab). In this study, we investigated whether LpMab-21 shows antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human podoplanin-expressing cancer cell lines in vitro and also studied its antitumor activities using a xenograft model. LpMab-21 showed high ADCC and CDC activities against not only podoplanin-expressing Chinese hamster ovary cells but also LN319 glioblastoma cells and PC-10 lung cancer cells, both of which endogenously express podoplanin. Furthermore, LpMab-21 decreased tumor growth in vivo, indicating that LpMab-21 could be useful for antibody therapy against human podoplanin-expressing cancers.

AB - The interaction between podoplanin (PDPN) and C-type lectin-like receptor 2 (CLEC-2) is involved in tumor malignancy. We have established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-21, one of the mouse antipodoplanin mAbs, is of the IgG2a subclass, and its minimum epitope was determined to be Thr76-Arg79 of the human podoplanin. Importantly, sialic acid is linked to Thr76; therefore, LpMab-21 is an antiglycopeptide mAb (GpMab). In this study, we investigated whether LpMab-21 shows antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human podoplanin-expressing cancer cell lines in vitro and also studied its antitumor activities using a xenograft model. LpMab-21 showed high ADCC and CDC activities against not only podoplanin-expressing Chinese hamster ovary cells but also LN319 glioblastoma cells and PC-10 lung cancer cells, both of which endogenously express podoplanin. Furthermore, LpMab-21 decreased tumor growth in vivo, indicating that LpMab-21 could be useful for antibody therapy against human podoplanin-expressing cancers.

KW - ADCC

KW - Antitumor activity

KW - CDC

KW - Monoclonal antibody

KW - Podoplanin

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U2 - 10.1089/mab.2016.0045

DO - 10.1089/mab.2016.0045

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SN - 2167-9436

VL - 36

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JO - Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

JF - Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

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ER -

Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity

Abstract

Keywords

UN SDGs

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