Back to Search
Start Over
A Humanized and Defucosylated Antibody against Podoplanin (humLpMab-23-f) Exerts Antitumor Activities in Human Lung Cancer and Glioblastoma Xenograft Models.
- Source :
-
Cancers . Oct2023, Vol. 15 Issue 20, p5080. 13p. - Publication Year :
- 2023
-
Abstract
- Simple Summary: Podoplanin (PDPN), also known as T1α/Aggrus/gp36, is a type I transmembrane sialo-glycoprotein that plays essential roles in cancer progression and metastasis. PDPN-expressing cancers show aggressive phenotypes, including increased stemness, invasiveness, and epithelial-to-mesenchymal transition, which lead to malignant progression. Furthermore, PDPN-positive cancer-associated fibroblasts mediate an immunosuppressive tumor microenvironment, which reduces antitumor immunity. Therefore, monoclonal antibodies (mAbs) against PDPN have been evaluated in preclinical models. In this study, we developed a humanized and defucosylated mAb against PDPN (humLpMab-23-f) and evaluated its antibody-dependent cellular cytotoxicity (ADCC) and antitumor effect in xenograft models of human tumor cells. humLpMab-23-f exerted antitumor activity against PDPN-overexpressed CHO-K1, endogenous PDPN-positive PC-10 (human lung squamous cell carcinoma), and LN319 (human glioblastoma) xenograft-inoculated mice. 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *THERAPEUTIC use of monoclonal antibodies
*THERAPEUTIC use of antineoplastic agents
*BIOLOGICAL models
*FLOW cytometry
*IN vitro studies
*XENOGRAFTS
*COMPLEMENT (Immunology)
*ANIMAL experimentation
*LUNG tumors
*GLIOMAS
*MEMBRANE glycoproteins
*GENE expression
*RESEARCH funding
*CELL lines
*CELL surface antigens
*SQUAMOUS cell carcinoma
*MICE
*IMMUNODIAGNOSIS
*CHEMICAL inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 15
- Issue :
- 20
- Database :
- Academic Search Index
- Journal :
- Cancers
- Publication Type :
- Academic Journal
- Accession number :
- 173269148
- Full Text :
- https://doi.org/10.3390/cancers15205080