A Humanized and Defucosylated Antibody against Podoplanin (humLpMab-23-f) Exerts Antitumor Activities in Human Lung Cancer and Glioblastoma Xenograft Models.
Hiroyuki SuzukiTomokazu OhishiMika K KanekoYukinari KatoPublished in: Cancers (2023)
A cancer-specific anti-PDPN mAb, LpMab-23 (mouse IgG 1 , kappa), was established in our previous study. We herein produced a humanized IgG 1 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.
Keyphrases
- squamous cell
- induced apoptosis
- endothelial cells
- squamous cell carcinoma
- flow cytometry
- monoclonal antibody
- cell cycle arrest
- induced pluripotent stem cells
- high glucose
- pluripotent stem cells
- papillary thyroid
- endoplasmic reticulum stress
- nuclear factor
- lymph node metastasis
- immune response
- radiation therapy
- high grade
- mesenchymal stem cells
- diabetic rats
- locally advanced
- psychometric properties
- smoking cessation