A Humanized and Defucosylated Antibody against Podoplanin (humLpMab-23-f) Exerts Antitumor Activities in Human Lung Cancer and Glioblastoma Xenograft Models-Reference-Cited by-同舟云学术

A Humanized and Defucosylated Antibody against Podoplanin (humLpMab-23-f) Exerts Antitumor Activities in Human Lung Cancer and Glioblastoma Xenograft Models

Published:2023-10-20 Issue:20 Volume:15 Page:5080
ISSN:2072-6694
Container-title:Cancers
language:en
Short-container-title:Cancers

Author:

Suzuki Hiroyuki¹²^ORCID,Ohishi Tomokazu³⁴^ORCID,Kaneko Mika K.¹²^ORCID,Kato Yukinari¹²^ORCID

Affiliation:

1. Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan

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

3. Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu-shi 410-0301, Shizuoka, Japan

4. Institute of Microbial Chemistry (BIKAKEN), Laboratory of Oncology, Microbial Chemistry Research Foundation, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan

Abstract

A cancer-specific anti-PDPN mAb, LpMab-23 (mouse IgG1, kappa), was established in our previous study. We herein produced a humanized IgG1 version (humLpMab-23) and defucosylated form (humLpMab-23-f) of an anti-PDPN mAb to increase ADCC activity. humLpMab-23 recognized PDPN-overexpressed Chinese hamster ovary (CHO)-K1 (CHO/PDPN), PDPN-positive PC-10 (human lung squamous cell carcinoma), and LN319 (human glioblastoma) cells via flow cytometry. We then demonstrated that humLpMab-23-f induced ADCC and complement-dependent cytotoxicity against CHO/PDPN, PC-10, and LN319 cells in vitro and exerted high antitumor activity in mouse xenograft models, indicating that humLpMab-23-f could be useful as an antibody therapy against PDPN-positive lung squamous cell carcinomas and glioblastomas.

Funder

Japan Agency for Medical Research and Development

Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Link

https://www.mdpi.com/2072-6694/15/20/5080/pdf

Reference36 articles.

1. Suzuki, H., Kaneko, M.K., and Kato, Y. (2022). Roles of Podoplanin in Malignant Progression of Tumor. Cells, 11.

2. Targeting a novel domain in podoplanin for inhibiting platelet-mediated tumor metastasis;Sekiguchi;Oncotarget,2016

3. Functional sialylated O-glycan to platelet aggregation on Aggrus (T1alpha/Podoplanin) molecules expressed in Chinese hamster ovary cells;Kaneko;J. Biol. Chem.,2004

4. Podoplanin: An emerging cancer biomarker and therapeutic target;Krishnan;Cancer Sci.,2018

5. Podoplanin promotes the invasion of oral squamous cell carcinoma in coordination with MT1-MMP and Rho GTPases;Li;Am. J. Cancer Res.,2015