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Development of Human Monoclonal Antibody for Claudin-3 Overexpressing Carcinoma Targeting

Title
Development of Human Monoclonal Antibody for Claudin-3 Overexpressing Carcinoma Targeting
Authors
Yang, HobinPark, HayeonLee, Yong JinChoi, Jun YoungKim, TaeEunRajasekaran, NirmalLee, SaehyungSong, KyoungHong, SungyoulChoi, Joon-SeokShim, HyunboKim, Young-DeugHwang, SoohyunChoi, Yoon-LaShin, Young Kee
Ewha Authors
심현보
SCOPUS Author ID
심현보scopus
Issue Date
2020
Journal Title
BIOMOLECULES
ISSN
2218-273XJCR Link
Citation
BIOMOLECULES vol. 10, no. 1
Keywords
claudintight junctionepithelial tumorhuman monoclonal antibody
Publisher
MDPI
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Most malignant tumors originate from epithelial tissues in which tight junctions mediate cell-cell interactions. Tight junction proteins, especially claudin-3 (CLDN3), are overexpressed in various cancers. Claudin-3 is exposed externally during tumorigenesis making it a potential biomarker and therapeutic target. However, the development of antibodies against specific CLDN proteins is difficult, because CLDNs are four-transmembrane domain proteins with high homology among CLDN family members and species. Here, we developed a human IgG1 monoclonal antibody (h4G3) against CLDN3 through scFv phage display using CLDN3-overexpressing stable cells and CLDN3-embedded lipoparticles as antigens. The h4G3 recognized the native conformation of human and mouse CLDN3 without cross-reactivity to other CLDNs. The binding kinetics of h4G3 demonstrated a sub-nanomolar affinity for CLDN3 expressed on the cell surface. The h4G3 showed antibody-dependent cellular cytotoxicity (ADCC) according to CLDN3 expression levels in various cancer cells by the activation of Fc gamma RIIIa (CD16a). The biodistribution of h4G3 was analyzed by intravenous injection of fluorescence-conjugated h4G3 which showed that it localized to the tumor site in xenograft mice bearing CLDN3-expressing tumors. These results indicate that h4G3 recognizes CLDN3 specifically, suggesting its value for cancer diagnosis, antibody-drug conjugates, and potentially as a chimeric antigen receptor (CAR) for CLDN3-expressing pan-carcinoma.
DOI
10.3390/biom10010051
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일반대학원 > 바이오융합과학과 > Journal papers
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