The mouse–canine chimeric anti-dog podoplanin antibody P38B exerts antitumor activity in mouse xenograft models

Yukinari Kato; Tomokazu Ohishi; Manabu Kawada; Naoya Maekawa; Satoru Konnai; Shunsuke Itai; Shinji Yamada; Mika K. Kaneko

Biochemistry and Biophysics Reports (Mar 2019)

The mouse–canine chimeric anti-dog podoplanin antibody P38B exerts antitumor activity in mouse xenograft models

Yukinari Kato,
Tomokazu Ohishi,
Manabu Kawada,
Naoya Maekawa,
Satoru Konnai,
Shunsuke Itai,
Shinji Yamada,
Mika K. Kaneko

Affiliations

Yukinari Kato: Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan; New Industry Creation Hatchery Center, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan; Corresponding author at: Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Tomokazu Ohishi: Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu-shi, Shizuoka 410-0301, Japan
Manabu Kawada: Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu-shi, Shizuoka 410-0301, Japan
Naoya Maekawa: Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan
Satoru Konnai: Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan; Laboratory of Infectious Diseases, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan
Shunsuke Itai: Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
Shinji Yamada: Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
Mika K. Kaneko: Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan

Journal volume & issue: Vol. 17
pp. 23 – 26

Abstract

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Podoplanin (PDPN) is a type I transmembrane heavily glycosylated sialoglycoprotein that is expressed in normal tissues such as pulmonary type I alveolar cells, renal podocytes, and lymphatic endothelial cells. PDPN overexpression in cancerous tissue is associated with hematogenous metastasis through interactions with the C-type lectin-like receptor 2 (CLEC-2). Previously, we have reported the development of a mouse monoclonal antibody (mAb), PMab-38 (IgG1, kappa) against dog PDPN (dPDPN). PMab-38 was found to strongly react with canine squamous cell carcinomas (SCCs) and melanomas; however, it showed no reaction with lymphatic endothelial cells. Recently, we have developed and produced the mouse–canine mAb of subclass B, P38B that showed antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against Chinese hamster ovary (CHO)/dPDPN cells. In the present study, we investigated the antitumor activity using mouse xenograft model. To induce ADCC activity by P38B, canine mononuclear cells were injected surrounding the tumors in a xenograft model. It was demonstrated that P38B exerted antitumor activity against the mouse xenograft model using CHO/dPDPN. These results suggest that P38B is useful for antibody therapy against dPDPN-expressing canine SCCs and melanomas. Keywords: Mouse-canine chimeric antibody, Dog podoplanin, dPDPN, Monoclonal antibody

Published in Biochemistry and Biophysics Reports

ISSN: 2405-5808 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General); Science: Chemistry: Organic chemistry: Biochemistry
Website: http://www.journals.elsevier.com/biochemistry-and-biophysics-reports/

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