Development of human monoclonal antibody for claudin-3 overexpressing carcinoma targeting

Hobin Yang, Hayeon Park, Yong Jin Lee, Jun Young Choi, Taeeun Kim, Nirmal Rajasekaran, Saehyung Lee, Kyoung Song, Sungyoul Hong, Joon Seok Choi, Hyunbo Shim, Young Deug Kim, Soohyun Hwang, Yoon La Choi, Young Kee Shin

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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 FcγRIIIa (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.

Original languageEnglish
Article number51
JournalBiomolecules
Volume10
Issue number1
DOIs
StatePublished - Jan 2020

Bibliographical note

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Claudin
  • Epithelial tumor
  • Human monoclonal antibody
  • Tight junction

Fingerprint

Dive into the research topics of 'Development of human monoclonal antibody for claudin-3 overexpressing carcinoma targeting'. Together they form a unique fingerprint.

Cite this