Phase I/II Clinical Trial of the Anti-Podoplanin Monoclonal Antibody Therapy in Dogs with Malignant Melanoma

Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan

Veterinary Medical Center, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan

Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan

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Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan

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New Industry Creation Hatchery Center, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Cells 2020, 9(11), 2529; https://doi.org/10.3390/cells9112529

Received: 29 September 2020 / Revised: 18 November 2020 / Accepted: 19 November 2020 / Published: 23 November 2020

(This article belongs to the Special Issue Structure and Function of Podoplanin (PDPN) in Disease)

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Abstract

Podoplanin (PDPN), a small transmembrane mucin-like glycoprotein, is ectopically expressed on tumor cells. PDPN is known to be linked with several aspects of tumor malignancies in certain types of human and canine tumors. Therefore, it is considered to be a novel therapeutic target. Monoclonal antibodies targeting PDPN expressed in human tumor cells showed obvious anti-tumor effects in preclinical studies using mouse models. Previously, we generated a cancer-specific mouse–dog chimeric anti-PDPN antibody, P38Bf, which specifically recognizes PDPN expressed in canine tumor cells. In this study, we investigated the safety and anti-tumor effects of P38Bf in preclinical and clinical trials. P38Bf showed dose-dependent antibody-dependent cellular cytotoxicity against canine malignant melanoma cells. In a preclinical trial with one healthy dog, P38Bf administration did not induce adverse effects over approximately 2 months. In phase I/II clinical trials of three dogs with malignant melanoma, one dog vomited, and all dogs had increased serum levels of C-reactive protein, although all adverse effects were grade 1 or 2. Severe adverse effects leading to withdrawal of the clinical trial were not observed. Furthermore, one dog had stable disease with P38Bf injections. This is the first reported clinical trial of anti-PDPN antibody therapy using spontaneously occurring canine tumor models. View Full-Text

Keywords: podoplanin; dog; antibody therapy; tumor; melanoma

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Kamoto, S.; Shinada, M.; Kato, D.; Yoshimoto, S.; Ikeda, N.; Tsuboi, M.; Yoshitake, R.; Eto, S.; Hashimoto, Y.; Takahashi, Y.; Chambers, J.; Uchida, K.; Kaneko, M.K.; Fujita, N.; Nishimura, R.; Kato, Y.; Nakagawa, T. Phase I/II Clinical Trial of the Anti-Podoplanin Monoclonal Antibody Therapy in Dogs with Malignant Melanoma. Cells 2020, 9, 2529. https://doi.org/10.3390/cells9112529

AMA Style

Kamoto S, Shinada M, Kato D, Yoshimoto S, Ikeda N, Tsuboi M, Yoshitake R, Eto S, Hashimoto Y, Takahashi Y, Chambers J, Uchida K, Kaneko MK, Fujita N, Nishimura R, Kato Y, Nakagawa T. Phase I/II Clinical Trial of the Anti-Podoplanin Monoclonal Antibody Therapy in Dogs with Malignant Melanoma. Cells. 2020; 9(11):2529. https://doi.org/10.3390/cells9112529

Chicago/Turabian Style

Kamoto, Satoshi, Masahiro Shinada, Daiki Kato, Sho Yoshimoto, Namiko Ikeda, Masaya Tsuboi, Ryohei Yoshitake, Shotaro Eto, Yuko Hashimoto, Yosuke Takahashi, James Chambers, Kazuyuki Uchida, Mika K. Kaneko, Naoki Fujita, Ryohei Nishimura, Yukinari Kato, and Takayuki Nakagawa. 2020. "Phase I/II Clinical Trial of the Anti-Podoplanin Monoclonal Antibody Therapy in Dogs with Malignant Melanoma" Cells 9, no. 11: 2529. https://doi.org/10.3390/cells9112529

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Phase I/II Clinical Trial of the Anti-Podoplanin Monoclonal Antibody Therapy in Dogs with Malignant Melanoma

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